DESC:FIELD OF THE INVENTION
[0001] The present invention relates to magnetic resonance imaging (MRI) contrast agents. Specifically, the present invention relates to smart nano-scaffolds as MRI contrast agents and method of preparation thereof. The present invention further relates to method of preparation of MRI contrast agents using nontoxic nanomaterials functionalized with non-toxic organic fragments via an aryl linker, optionally along with gene targeting moiety. The present invention further relates to use of smart nano-scaffolds based MRI contrast agents in early detection of cancer or brain tumor.
BACKGROUND OF THE INVENTION
[0002] Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
[0003] Nanomaterial’s play important role in the development of highly efficient contrast agents (CAs). Many researchers have invested their efforts on various nanomaterial, such as Iron (Fe), Manganese (Mn), and Platinum (Pt), based CAs due to their capacity to enhance the MRI signal at lower concentration, have potential for long blood circulation, and responsiveness to different biochemical environment. Recently, Macher et al and many others (Adv. Funct. Mater. 2015, 25, 490-494) used the ultrathin iron oxide nanomaterial’s as a positive (T1) contrast agent for magnetic resonance imaging (MRI) and images showed significant brightening compare to water surroundings. Other than Fe based CAs, few other metal ions, namely, high spin Mn(II), high spin Mn(III), and Eu(II), that can serve as effective relaxation agents. Due to low charge to radius ratio of Mn (II) complexes, they possess lower stability and kinetic inertness. High spin Mn(III) complexes such as Mn-porphyrin and Mn complexes of 1,2-phenylenediamine derived bis-amidate ligands (Mn-PDA) have also been demonstrated as effective MRI contrast agents (J. Am. Chem. Soc. 2016, 138, 5483-5486). The Mn-PDA complexes were shown to be cell permeable and have been further elaborated for detection of intracellular enzymes. These results have motivated researchers to investigate the impact of various formulations of nanomaterials on MRI contrast.
[0004] In last couple of years, several reports have been emerging showing the potential of nanomaterials in MRI. Yang et al. (Nano Lett. 2019, 19, 441-448) utilized commercially available Gd-DOTA complex to functionalize with polyethylene glycol (PEG) and then incorporated into graphene quantum dots to obtain ?paramagnetic graphene quantum dots. The relaxivity of this new material was much higher than the market available GBCA. Similarly, many renowned researchers in the field of nanotechnology have developed MRI contrast agents based on proteins, liposomes, dendrimers, and graphenes with better efficiency and relaxivity.
[0005] Even after vigorous development in the field of contrast agents, the main problems such as short circulation time, low relaxivity, and little or no specificity, remains the same. One of the major challenges in the field of MRI CAs is to improve the contrast for sensitive molecular imaging while minimizing the concentration of Gd3+. Therefore, novel compounds which own strong proton relaxivity or provide better contrast for MR signal enhancement at lower doses are required.
[0006] The major challenges in the field of MRI CAs are to improve the contrast for sensitive molecular imaging while minimizing the concentration of Gd3+ and improving the toxicity profile of CAs utilizing non-toxic metals. Activable contrast agents, whose signal is altered by pH, enzymatic activity, temperature change, or ion flux, represent an exciting and growing area of research. New contrast agents with the capability to detect or quantify pathologic biomarkers that could revolutionize the specificity with which MRI can be used to detect, characterize, and quantify pathologic tissue are the need of the hour.
[0007] Therefore, novel compounds which own strong proton relaxivity or provide better contrast for MR signal enhancement at lower doses are required. Hence, there is a great potential to create contrast agents that are biochemically targeted and potentially more specific to disease. There is, therefore, a need to develop new and more efficient MRI contrast agents that can overcome deficiencies associated with the known arts.

OBJECTS OF THE INVENTION
[0008] An object of the present invention is to provide contrast agents that satisfies the existing needs, as well as others, and generally overcomes the deficiencies found in the prior art.
[0009] Another object of the present invention is to provide contrast agents that have improved circulation time and are specific in action.
[0010] Yet another object of the present invention is to provide contrast agents having improved contrast for sensitive molecular imaging at lower doses.
[0011] Another object of the present invention is to provide contrast agents having strong proton relaxivity.
[0012] Another object of the present invention is to provide contrast agents that can be prepared by using non-toxic materials.
[0013] Another object of the present invention is to provide contrast agents that are more specific to disease.
[0014] The other objects and preferred embodiments and advantages of the present invention will become more apparent from the following description of the present invention when read in conjunction with the accompanying examples and figures, which are not intended to limit scope of the present invention in any manner.

SUMMARY OF THE INVENTION
[0015] This summary is provided to introduce a selection of concepts in a simplified form that are further described below in Detailed Description section. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.
[0016] The present invention relates to magnetic resonance imaging (MRI) contrast agents. Specifically, the present invention relates to smart nano-scaffolds based MRI contrast agents and method of preparation thereof.
[0017] In one aspect, the present invention relates to smart nano-scaffolds based MRI contrast agents prepared using nontoxic nanomaterials functionalized with non-toxic organic fragments via an aryl linker, optionally along with gene targeting moiety.
[0018] In another aspect, the present invention relates to smart nano-scaffolds based MRI contrast agents wherein nontoxic nanomaterials are bio-friendly quantum dots of glucose, graphene or carbon and/or boron nanotube surface.
[0019] In another aspect, the present invention relates to smart nano-scaffolds based MRI contrast agents wherein non-toxic organic fragments are amine fragment and/or carbohydrate.
[0020] According to aspects of the present invention, carbohydrate includes glucose, fructose, ribose, glucosamine and the like.
[0021] In a preferred aspect, the present invention relates to smart nano-scaffolds based MRI contrast agents wherein non-toxic amine fragment is ethylene diamine.
[0022] In another aspect, the present invention relates to smart nano-scaffolds based MRI contrast agents wherein linker is ethylene diamine or anhydride based organic fragment.
[0023] In another aspect, the present invention relates to smart nano-scaffolds based MRI contrast agents wherein amine fragment and/or carbohydrate serve as chelating partner for metal.
[0024] In another aspect, the present invention relates to smart nano-scaffolds based MRI contrast agents wherein chelated metal can be selected from Iron (Fe), Platinum (Pt), Manganese (Mn) or Copper (Cu), preferably Iron.
[0025] In another aspect, the present invention relates to smart nano-scaffolds based MRI contrast agents wherein gene targeting moiety is nucleosides or nucleotides or DNA or RNA or aptamer or oligonucleotide.
[0026] In one aspect, the present invention relates to smart nano-scaffolds based MRI contrast agents prepared using nanomaterial support and non-toxic metal.
[0027] In another aspect, the present invention relates to use of smart nano-scaffolds based MRI contrast agents in early detection of cancer or brain tumor.
[0028] In another aspect, the present invention relates to use of smart nano-scaffolds based MRI contrast agents having improved contrast for sensitive molecular imaging at lower doses.
[0029] In another aspect, the present invention relates to use of smart nano-scaffolds based MRI contrast agents having strong proton relaxivity.
[0030] In another aspect, the present invention relates to method of preparation of smart nano-scaffolds based MRI contrast agents.
[0031] In another aspect, the MRI contrast agents of the present invention can be prepared by the process comprising the steps of:
a) Synthesizing metal complex using linker fragment;
b) Synthesizing organic framework using metal complex; and
c) Synthesizing smart MRI contrast agent on nanomaterials.

[0032] Other aspects of the invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learnt by the practice of the invention.

BRIEF DESCRIPTION OF DRAWINGS THE INVENTION
[0033] The following drawings form part of the present specification and are included to further illustrate aspects of the present disclosure. The disclosure may be better understood by reference to the drawings in combination with the detailed description of the specific embodiments presented herein.
Figure 1: Synthetic sequence for preparing smart nano-scaffolds based MRI contrast agents.

DETAILED DESCRIPTION
[0034] The following is a detailed description of embodiments of the disclosure. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure as defined by the appended claims.
[0035] All publications herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
[0036] Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.
[0037] In some embodiments, the numbers expressing quantities of ingredients, properties such as concentration, reaction conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in some instances by the term “about.” Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
[0038] As used in the description herein and throughout the claims that follow, the meaning of “a,” “an,” and “the” includes plural reference unless the context clearly dictates otherwise. Also, as used in the description herein, the meaning of “in” includes “in” and “on” unless the context clearly dictates otherwise.
[0039] Unless the context requires otherwise, throughout the specification which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense that is as “including, but not limited to.”
[0040] The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g. “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.
[0041] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.
[0042] The description that follows, and the embodiments described therein, is provided by way of illustration of an example, or examples, of particular embodiments of the principles and aspects of the present disclosure. These examples are provided for the purposes of explanation, and not of limitation, of those principles and of the disclosure.
[0043] It should also be appreciated that the present disclosure can be implemented in numerous ways, including as a system, a method or a device. In this specification, these implementations, or any other form that the invention may take, may be referred to as processes. In general, the order of the steps of the disclosed processes may be altered within the scope of the invention.
[0044] The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments.
[0045] The following discussion provides many example embodiments of the inventive subject matter. Although each embodiment represents a single combination of inventive elements, the inventive subject matter is considered to include all possible combinations of the disclosed elements. Thus if one embodiment comprises elements A, B, and C, and a second embodiment comprises elements B and D, then the inventive subject matter is also considered to include other remaining combinations of A, B, C, or D, even if not explicitly disclosed.
[0046] Various terms as used herein are shown below. To the extent a term used in a claim is not defined below, it should be given the broadest definition persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of filing.
[0047] The present invention relates to magnetic resonance imaging (MRI) contrast agents. Specifically, the present invention relates to smart nano-scaffolds based MRI contrast agents and method of preparation thereof.
[0048] In one embodiment, the present invention relates to smart nano-scaffolds based MRI contrast agents prepared using nontoxic nanomaterials functionalized with non-toxic organic fragments via an aryl linker, optionally along with gene targeting moiety.
[0049] In another embodiment, the present invention relates to smart nano-scaffolds based MRI contrast agents wherein nontoxic nanomaterials are bio-friendly quantum dots of glucose, graphene or carbon and/or boron nanotube surface.
[0050] In another embodiment, the present invention relates to smart nano-scaffolds based MRI contrast agents wherein non-toxic organic fragments are amine fragment and/or carbohydrate.
[0051] According to embodiments of the present invention, carbohydrate includes glucose, fructose, ribose, glucosamine and the like.
[0052] In a preferred embodiment, the present invention relates to smart nano-scaffolds based MRI contrast agents wherein non-toxic amine fragment is ethylene diamine.
[0053] In another embodiment, the present invention relates to smart nano-scaffolds based MRI contrast agents wherein linker is ethylene diamine or anhydride based organic fragment.
[0054] In another embodiment, the present invention relates to smart nano-scaffolds based MRI contrast agents wherein amine fragment and/or carbohydrate serve as chelating partner for metal.
[0055] In another embodiment, the present invention relates to smart nano-scaffolds based MRI contrast agents wherein chelated metal can be selected from Iron (Fe), Platinum (Pt), Manganese (Mn) or Copper (Cu), preferably Iron.
[0056] In another embodiment, the present invention relates to smart nano-scaffolds based MRI contrast agents wherein gene targeting moiety is nucleosides or nucleotides or DNA or RNA or aptamer or oligonucleotide.
[0057] In one embodiment, the present invention relates to smart nano-scaffolds based MRI contrast agents prepared using nanomaterial support and non-toxic metal.
[0058] In another embodiment, the present invention relates to use of smart nano-scaffolds based MRI contrast agents in early detection of cancer or brain tumor.
[0059] In another embodiment, the present invention relates to use of smart nano-scaffolds based MRI contrast agents having improved contrast with relaxivity of r2 = ~20.1 for sensitive molecular imaging.
[0060] According to embodiments of the present invention, the MRI contrast agents of the present invention exhibit a relaxation with r2 = 20.1 at a dose of 0.5 mg/kg.
[0061] In another embodiment, the present invention relates to use of smart nano-scaffolds based MRI contrast agents prepared using non-toxic biofriendly materials such as cane sugar bagasse.
[0062] In another embodiment, the present invention relates to use of smart nano-scaffolds based MRI contrast agents having strong proton relaxivity with 4-fold increase in the relaxation values as compare to the spherical iron nanoparticles.
[0063] In another embodiment, the present invention relates to method of preparation of smart nano-scaffolds based MRI contrast agents comprising the steps of:
a) Synthesis of organic framework bearing gene targeting moiety via nucleophilic substitution, condensation, and reduction protocols;
b) Synthesis of bio-friendly graphene nanomaterial’s using Adenosine, cytosine, thymidine, and guanine; and
c) Reaction of organic framework and synthesis of nanomaterial to yield smart nanomaterial.
[0064] In another embodiment, the present invention relates to design and fabrication of gene and metal decorated organic linker via state of art chemical synthesis.
[0065] In yet another embodiment, the present invention relates to synthesis of non-toxic quantum dots (QD) of glucose and graphene surface by using carbohydrates and nucleic acids.
[0066] In yet another embodiment, the present invention relates to synthesis of non-toxic quantum dots by the hydrothermal treatment of glucose at 160 oC for 12 hours followed by cooling and freeze drying. The obtained carbon-dots were analyzed by UV-Vis and Infrared spectroscopy.
[0067] In still another embodiment, the present invention relates to development of Boron carbon nanotubes as potential surface for contrast agent incorporation.
[0068] In another embodiment, the present invention relates to incorporation of pro- contrast agents onto surface modified nanomaterials via esterification reaction.
[0069] In yet another embodiment, the present invention relates to investigation of stability and toxicity of newly developed metal-containing complexes under physiological condition.
[0070] In still another embodiment, the present invention relates to characterization of the in-vitro imaging properties of smart nano-materials against HeLa cell lines.
[0071] In another embodiment, the present invention relates to a novel platform for the fabrication of Fe anchored contrast agents carrying gene targeting moiety linked with non-toxic anhydride based linker.
[0072] Macrocyclic complexes of Fe(II), Fe(III), Pt(II), and their nanoparticles has been used in MRI due to their paramagnetic character. Iron and platinum nanoparticles have also received considerable attention for their imaging properties. However, iron and platinum complexes suffers from low intracellular stability and toxicity.
[0073] In one embodiment of the present invention, appending the iron (Fe) and platinum (Pt) metals onto graphene and related surfaces brings stability to the complexes. Moreover, graphene surface will provide stacking interactions for the metal, which will boost the intracellular stability of contrast agents.
[0074] In another embodiment of the present invention, length of the linker and ligand is important from stability and relaxivity point of view. Length optimization of linker is significant, as it plays an important role in the steric hindrance. It has been observed that the relaxivity of contrast agent is depending upon the size and rotation of molecule in the field. Anchoring of contrast agents onto the nanomaterial surface will make the whole system of large molecular weight and high steric hindrance, which will slow down the rotational motion of the complex and hence the resultant relaxivity will improve.
[0075] In one embodiment, the present invention relates to graphene quantum dot/boron-carbon nanotube based MRI contrast agent with iron and/or platinum metals for good relaxivity.
[0076] In another embodiment, the present invention relates to linkage of gene targeting moiety with paramagnetic molecule bearing iron and platinum via coordination bond.
[0077] Currently, there is no reliable way to detect primary liver cancer and hepatic metastases at early stages with high sensitivity and specificity, which is a severe limitation of contrast agents. The present invention discloses the gene targeted MRI contrast agents with tunable feature depending on the target cancer cell. Due to large number of metal-ligands incorporated onto graphene surface, contrast agent will achieve better localization and imaging properties at low dose concentration.
[0078] In one embodiment of the present invention, Figure 1 discloses the synthetic sequence for preparing contrast agents of the present invention, wherein
a) Organic framework is attached to graphene quantum dot and/or graphene surface and/or boron nanotube surface by means of covalent bond;
b) Non-toxic linker could be the derivative of ethylenediamine and/or carbohydrate, where X = O, N, S;
c) Metal attached to the non-toxic linker is not limited to Iron (Fe) and Platinum (Pt) and could extend to Manganese (Mn) and Copper (Cu);
d) Gene targeting moiety could be DNA, RNA, Aptamer, oligonucleotides, nucleobase, nucleotide, etc.
[0079] In another aspect, the present invention relates to method of preparation of smart nano-scaffolds based MRI contrast agents.
[0080] In yet another embodiment, the MRI contrast agents of the present invention can be prepared by the process comprising the steps of:
a) Synthesizing metal complex using linker fragment;
b) Synthesizing organic framework using metal complex; and
c) Synthesizing smart MRI contrast agent on nanomaterials.

[0081] In still another embodiment, the MRI contrast agents of the present invention are prepared wherein pro- contrast agents are incorporation onto surface modified nanomaterials via esterification reaction.
[0082] In another embodiment of the present invention, MRI contrast agent and/or drug delivery vehicle are used in early detection of cancer and/or detection of any brain tumor.
[0083] In another embodiment, the present invention provides contrast agents that demonstrate better renal clearance of iron and platinum.
[0084] In another embodiment, the present invention provides contrast agents that offer better stability in vivo under acidic media.
[0085] While the foregoing describes various embodiments of the disclosure, other and further embodiments of the disclosure may be devised without departing from the basic scope thereof. The scope of the invention is determined by the claims that follow. The invention is not limited to the described embodiments, versions or examples, which are included to enable a person having ordinary skill in the art to make and use the invention when combined with information and knowledge available to the person having ordinary skill in the art.
EXAMPLES
[0086] The present invention is further explained in the form of following examples. However, it is to be understood that the following examples are merely illustrative and are not to be taken as limitations upon the scope of the invention.
[0087] Example 1: Synthesis of metal complex of ethylenediamine derivatized fragment
[0088] The metal complex of ethylenediamine derivatized fragment is synthesized as shown in Scheme 1 following the below mentioned process steps:
[0089] Step-1: Reaction of m-nitrobenyzl bromide 1 with N1-(2-aminoethyl)ethane-1,2-diamine 2 in presence of base such as triethyl amine results in nucleophilic substituted product N1-(2-aminoethyl)-N2-(3-nitrobenzyl)ethane-1,2-diamine 3.
[0090] Step-2: Condensation of imidazole-2-carbaldehyde 4 with amine derivative 3 affords nitrogen-functionalized scaffold bearing heterocyclic moiety 5.
[0091] Step-3: Iron metal is coordinated with the organic moiety 5 by using FeCl3 to form metal coordination complex 6.
[0092] Step-4: Metal coordination complex 6 is then reduced to its amine derivative by using Lewis acidic metal in acetic acid to afford the metal complex 7.

Scheme 1

[0093] Example 2: Synthesis of organic framework bearing metal complex.
[0094] The organic framework is synthesized using the metal complex synthesized in Example 1 using the below mentioned process steps. The synthetic scheme is illustrated in Scheme 2.
[0095] Step-5: Synthesis of organic framework starts from (2-hydroxy-5-methyl-1,3-phenylene)dimethanol 8. Compound 8 is treated with tert-butyldimethyl silyl chloride to afford hydroxyl-protected phenylene 9.
[0096] Step-6: Monodeprotection of compound 9 in presence of 0.5 equivalent of tetrabutylammonium fluoride (TBAF) results in 2-([(tert-Butyldimethylsilyl)oxy]methyl)-6-(hydroxymethyl)-4-methylphenol 10.
[0097] Steps-7 & 8: Reaction of primary alcohol of compound 10 with succinic anhydride 11 followed by treatment with N-hydroxysuccinimide (NHS, 13) results in activated ester 14.
[0098] Step-9: Metal complex compound 7 is then reacted with activated ester 14 to afford TBDMS protected metal organic framework 15.
[0099] Step-10: Deprotection of primary alcohol of compound 15 by using TBAF gives free alcohol 16, which serves as platform to hook gene-targeting moiety.

Scheme 2
[00100] Example 3: Synthesis of smart MRI contrast agent on graphene quantum dot
[00101] Step-11: Organic framework bearing metal 16 undergoes esterification reaction with Graphene Quantum dots (GDQ) 17 in the presence of dicyclohexyl carbodiimide (DCC) to form final conjugate compound 18 that serves as MRI contrast agent, as illustrated in Scheme 3.

Scheme 3

[00102] The foregoing examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention.

ADVANTAGES OF THE PRESENT INVENTION
[00103] The present invention provides contrast agents that can be prepared by using non-toxic materials.
[00104] The present invention provides contrast agents that offer better stability in vivo under acidic media.
[00105] The present invention provides contrast agents that demonstrate easy to achieve site-specific localization of MRI agents.
[00106] The present invention provides contrast agents that have improved circulation time and are specific in action.
[00107] The present invention provides contrast agents having improved contrast for sensitive molecular imaging at lower doses.
[00108] The present invention provides contrast agents having strong proton relaxivity.
[00109] The present invention provides contrast agents that are more specific to disease.
[00110] The present invention provides contrast agents that demonstrate better renal clearance of iron and platinum.

,CLAIMS:1. A smart nano-scaffold based MRI contrast agent, for early detection of cancer or brain tumor, comprising nontoxic nanomaterials functionalized with non-toxic organic fragments via an aryl linker, optionally along with gene targeting moiety, wherein the linker is a derivative of ethylene diamine or anhydride based organic fragment.
2. The MRI contrast agent as claimed in claim 1, wherein nontoxic nanomaterials are bio-friendly quantum dots of glucose, graphene or carbon and/or boron nanotube surface.
3. The MRI contrast agent as claimed in claim 1, wherein non-toxic organic fragments are amine fragment or carbohydrate that serve as chelating partner for metal.
4. The MRI contrast agent as claimed in claim 3, wherein chelated metal can be selected from Iron (Fe), Platinum (Pt, Manganese (Mn) or Copper (Cu), preferably Iron.
5. The MRI contrast agent as claimed in claims 1 and 3, wherein the amine is ethylene diamine.
6. The MRI contrast agent as claimed in claims 1 and 3, wherein carbohydrate is selected from glucose, fructose, ribose or glucosamine.
7. The MRI contrast agent as claimed in claim 1, wherein gene targeting moiety is selected from nucleosides, nucleotides, DNA, RNA, aptamer or oligonucleotide.
8. The MRI contrast agent as claimed in claims 1 and 2, wherein non-toxic quantum dots are prepared by the hydrothermal treatment of glucose at 160 oC for 12 hours followed by cooling and freeze drying.
9. The MRI contrast agent as claimed in claims 1-8, having improved contrast with relaxivity of r2 = ~20.1 for sensitive molecular imaging.
10. The MRI contrast agent as claimed in claim 9, which exhibit a relaxation with r2 = 20.1 at a dose of 0.5 mg/kg.
11. The MRI contrast agent as claimed in claims 1-8, prepared using non-toxic biofriendly materials such as cane sugar bagasse.
12. A method for preparation of smart nano-scaffolds based MRI contrast agents, as claimed in claims 1-11, comprising the steps of:
a) Synthesizing metal complex using linkxer fragment;
b) Synthesizing organic framework bearing metal complex; and
c) Synthesizing smart MRI contrast agent on nanomaterials;
wherein pro-contrast agents are incorporation onto surface modified nanomaterials via esterification reaction.