INTRODUCTION:

Nanotechnology circumscribes a wide dimension of apparatus, expertise, applications and is considered to be one of the best breakthroughs of the 21st century. It is the development of wide range of materials, tools which involves the manipulation at an exceedingly small level ranging between 1-100 nm.^1,2The high surface to volume ratio is the phenomenon cause behind the distinctive physiochemical and surface properties. It ultimately gives material their novel properties and an upper hand over the conventionally used technologies.^3-6

Today the nanotechnology has become the buzzword of the various academician, researcher and media people which have seen a huge flow of investment not only from the government but also from the private investor.

Cancer nanotechnology is one such area of works which involves biology to chemistry, medicine, engineering, and has emerged as a new field of development.^7,8Under the Nano creation, the detection, imaging, and treatment of cancer have taken a quantum leap. The basic ideology is the utilization of never seen property of nanoparticles like optical, electronic and magnetic in order to quantify the tumors or to act as the contrasting agent.⁹ The Recent proceeding has led to the development of conjugated nanoparticle with peptide, protein and bio component for specific binding and higher retention.^10-16

THE PROBLEM OF CANCER:

Cancer is one of the deadly diseases known to the human beings today. It is responsible for mind-boggling problem created throughout the society. It is basically the result of conversion of proto-oncogene into oncogene which is an altered gene that has no control over cell division. Two hundred different types of cancer are known today. There are various researches going in these fields to overcome this dangerous, life-threatening disease which is claiming the lives of innocent people worldwide.

It is rather difficult to understand and the reason behind this is genetic instability and assembling of varied modifications at the molecular level.^17,18 The currently available technology has the room full of flaws leading from the failure in the mapping of the complete heterogeneity of tumor and insufficiency in prognostication of the outcome and the course of treatment. The biggest disadvantage of conventional medication in the field is treating both healthy and diseased cells in the same container which led to the wide range of toxicity and the adverse effect.^19,4 While the other problems include the late diagnosis of cancer which has already made the matter more worse. By that stage, the cancer cell has already invaded and metastasized at many different location. And then at this stage comes the limit to the effectiveness of the therapeutic agents.²⁰ Well today there is lot of research is going on in this particular field while the prominent one are the development of apparatus for the tumor imaging and early detection, (b) newer ways in the identification and the diagnostic approaches (c) ways to deal with the toxicity and harmful effect of administered drug through the conventional ways.⁷⁶

CANCER BIOMARKER:

Biomarkers can be defined as any biological components or the biomolecules or analytical traits that can be associated with the disease or its behavior. There are various example or the components which fall under this category like metabolite molecules, RNAs mutant gene, proteins, lipids etc.^21-32 These are estimated on the basis of their co-relation and molecular profiling along with the cancer behavior at the different time frame. It has been predicted that this understanding of biomarkers can lead us to know about the aggressive behavior or phenotypes and it will help us not only in the diagnosis of cancer but also it will lead to the personalized and predictive medicine. Golub et.al were the first to do molecular profiling and said tumor could be classified on the basis of the gene expression and this new insight was later on validated by finding that it is the sum total of a tumoral, stomal and inflammatory factor.³³ Later on, Perou et al. and Bittner et al. have validated the concept of the specific molecular portrait.^34-37 The latest work in this field is done by Rubin, Chinnaiy and their co-workers who have combined the cDNA microarrays in collaboration with the tissue microarrays for biomarker discovery. They are the best teller of cancer stage, as for how far they have spread and they are also androgen independent.^38-39

PERSONALIZED MEDICINE:

To work on the individual basis, the molecular profiling has led the way. The biomarkers are key to the very characterization of cancer and to quantify the limits to which it has been extended to the body.^41-43 one example of it is the person having high level of prostate specific antigen expressed in body makes the person to be more vulnerable to the prostate cancer. While in future, we can check the other marker along with the PSA marker and gives drug according to it. Which can at the same time provide precise identification, this is the foundation of the personalized oncology and it is expected to increase the effectiveness and specificity while reducing the dosage of the therapeutic agent. Although we had a great deal of the advances, still everything is strangled. Provided the bottleneck of the majority of the work is the highly heterogeneous tumor. Containing the variety of the cells like stromal, benign and cancerous cell which is the dead-end of all the conventional technologies like of RT-PCR, gene chips, protein chips, etc. Furthermore, their requirement of cells or the tissue destructive preparation lead to the loss of valuable 3D cellular information.^44,45,76

NANOPARTICLES PROBE:

Quantum dot is the nanoparticle with the quantum confinement properties in the entire three dimensions and often is made up of the semiconductor. It has the great role to play in the in vivo imaging.^46-50 These are the new class of the probe nanoparticle which has an indispensable role to be played as the fluorescence probes. The biggest advantage of it is the use of quantum dots in imaging accounting to their unique optical and the electrical properties. Another reason why it is becoming favorable is because of 10 to 15 time’s higher molar extinction coefficient as compare of the organic dyes along with the size-tunable emission. Their ability to work at the near-infrared wavelength has cut down the limitation of the tissue penetration and disturbance in collection due to the background fluorescence.⁵¹ They are also preferred cause they have the specific color for the specific size, for example, CdSe/ZnS quantum dots of approximately 20 nm gives the blue color while that of 7nm gives the red color.⁵²

This has given the idea of creation of smart nanoparticle and also led to the foundation of multiplex imaging cause of the broad absorption range and narrow emission peaks of the quantum dots. For example taking the contrasting agents along with the similar size of oxide, the nanoparticle has lead to the creation of dual probe. This multiplex diagnosis and imaging have opened new field of research. Researchers have been constantly working on the creation of probes which has bio-recognition molecules in order to increase the specificity and the sensitivity. Quantum dots even though having relatively large hydrodynamic radii suffer the lesser amount of kinetic or steric hindrance.⁵³

MOLECULAR CANCER IMAGING:

Techniques like positron emission tomography (PET) uses radioactive small molecules, so is the scenario with single photon emission computed tomography. They acts as the differentiating agent and does the in-vivo treatment and imaging with the help of gadolinium compound like in MRI which is soon going to be history for quite a few reasons.

Quantum dot the replacement of the organic dyes and fluorescence agents are the future of the imaging cause of their smaller size and the largest surface to volume ratio accounting for quite particular and different properties like optical, magnetic and structural properties as compared to the conventional dyes.⁷⁶ Not only that, their properties like optical and electrical can be changed with the size since it’s all about the size hence it can be very specific in their result. Second, their larger surface areas can be instrumental in binding it with various analyte so that it can be broader in its approach at the same time we can encapsulate it with a therapeutic agent. This provides us the opportunity to make smart nanoparticle a reality. Where these particles having the broad absorption range meanwhile it also has the advantage of narrow emission peaks of quantum dots giving it specificity too.^56,57 Another reason why it’s time to bid farewell to organic dyes is a large amount of it being simply ejected out. While quantum dot has the ability of accumulation of particle at the tumor sites and the phenomenon is known as the enhanced permeability and the retention (EPR). This owes its foundation to the absence of the effective lymphatic, drainage system and to the abnormal growth factor-like vascular endothelial.^54-57

PROBE DESIGN:

Quantum dots are fast in the processing as well as they show highly magnified result. They work in such a manner that can detect even the slightest presence of the analytes in the sample. They are almost 50x brighter than that of the organic dyes.^46,47 The probes are basically designed in 15-18 nm range. In which the core nanocrystal is surrounded by the inorganic shell and then further organic coatings. The inorganic shell leads to the improvement in the brightness and the stability while the water solubility is a function of the layers of organic coated over it and the functional group provides the ability to adhere or to conjugate. Besides these, the two-layer also help to escape the (RES) Reticuloendothelial system, increases the retention time and also decreases the toxicity by encapsment.^24-32

One such example was stated by Gao et al. in which the drug delivery and targeting principle form the basis of in vivo cancer targeting and imaging ^58,
59. The core-shell of CdSe/ZnS has been protected by the twin layer of the coordinating ligand and an amphiphilic polymer. Tri-n-octyl phosphine oxide (TOPO) has been used by them in order to create a hydrophobic interaction to protect from the enzymatic degradation and hydrolysis even in the complex in vivo condition.^24,25,60

Polybutyacrylate and polyethylacrylic are the two hydrophobic segment followed by the hydrophilic segment that is the polymethylacrylic acid segment and further followed by the hydrophobic and hydrocarbon side chain. The key finding of Gao et al. was the TOPO capped quantum dots which can disperse at the same time and encapsulate via a spontaneous self-assembly. While linking with a polymer like polyethylene glycol (PEG) molecule are protected to such an extent that their properties do not even change when treated in the wide range of the pH. This has also lead to the enhancement in the bio-compatibility and circulation.^61-63

Josephson and shows the coworker took MRI as the better equipment for the tomography and also in the imaging. They have worked over the probes with the dual modality which can use as the contrasting agents in the MRI while at the same time as the imaging agent. In pursuit of which they have created super magnetic Iron oxide nanoparticle in the collaboration with the fluorescent dye Cy5.5 which can go into the binding with the apoptotic cell and are detectable by both the MRI and the fluorescence.^64,65

The other has taken under the consideration Fe2O3 and FePt to create new dual-mode nanoparticle while some other researcher hasalso takenGd on the quantum dot to form the dual probe. Nie et al. have created the cluster of the paramagnetic gadolinium chelates to polymer coated quantum particles and the clinical trial has lead to the conclusion that it is biocompatible and can be valid in the MRI and shows the fluorescence. The favorable result was that they showed excellent properties without being the hindrance to the other.^66,67

LIPOSOMES FOR IMAGING:

Liposomes have emerged as the carrier for the contrast agent to be delivered as well as the radiopharmaceutical. Koo et al. have developed 99m Tc-liposomes for the imaging through SPECT.^68,69They used the sterically stabilized liposomes (SSCs) encapsulating 99m Tc-HMPAO in two of the form that is VIP ligand which is bounded covalently in one case and not bound in the other.⁷⁰ As a result, they have observed that the VIP ligand bound SSC has been accumulated in the larger amount as compared to the one which is not covalently bound. Since the tumor region is leaky and has VIP receptor expressed leading to the preferential accumulation as compared to other where both the situation does not exist hence any accumulation.^68-70

MAGNETIC NANOPARTICLE FOR IMAGING:

There is a quite significant discovery in the field of the MRI contrast agent. The recent is the colloidal iron oxide along with dextra. However, the limited tissue targeting and higher toxicity are the cause of the cellular internalization and subsequent cell disruption. But it is experimented and found that the coupling of the insulin over the nanoparticle can help to reduce the toxicity by decreasing cellular internalization of the nanoparticle in vitro.⁷¹ At the same time polyacrylamide with surface PEG and also the SLPs (solid lipid nanoparticle) provides an opportunity to iron oxide nanoparticle to get embedded into it and when these are injected as part of the experiment it was found that there is increase in relativity and circulation half-life.

TUMOR TARGETING:

Active targeting and passive targeting are the two methods through which quantum dots are administered in-vivo to tumors. There is the preferential accumulation of quantum dot nanoparticle at tumor site owing to the enhanced permeability and the retention factor of it.^62,63,77.The phenomenon accounts for the two main reasons in which the former one is angiogenic tumor production which further led to the expressed vascular endothelial growth factor that can be seen as a way to hyper permeabilize the tumor-associated by nanovasculature. While the latter one is the tumor limitation i.e. not having the effective lymphatic drainage system that can lead to the effective macromolecule accumulation.^72,73

Gao et al. have redefined the active targeting by the creation of the nanoparticle which is conjugated to the antibody in order to target the prostate-specific membrane antigen (PSMA).⁷⁴ Accumulation at the site of the tumor is the basis of radioimmunoscint graphic scanning.⁷⁵ They went on to develop a new class of probe designed in such a manner that it can lead to the multiplex imaging. It was conjugated to the amphiphitic triblock copolymer that provides protection to the core-shell and also decreases the chances of degradation and reduction in the properties. The functional group bounded provides the specific recognition sites. Further moving on Gao et al. tried to investigate the behavior of QD-PSMA Ab, QD-PEG, AND QD-COOH in the uptake followed by the retention or the board clearance. As a result, they have found that non-specific QD uptake and accumulation occur primarily in the liver or spleen. While the QD which had the COOH group has shown no tumor targeting and also it has been the first one to be cleared. While the one coated with the PEG showed the larger time of retention in the blood and the organ uptake was reduced and when QD encapsulated PEG and bioconjugated at the same time by PSMA Ab, they were more specific and the enhanced tumor targeting is seen but the apparent accumulation was in the liver along with the spleen.

IN-VIVO CANCER IMAGING:

Gao et al. injected the QD-PSMA Ab probes into the tail of the mouse that had the tumor and in the control mouse with no tumor.⁵³ And they have observed that the QD signals along with the autofluorescence of background with the help of spectral unmixing of the algorithm, and they were able to obtain the two different imaging of autofluorescence and the QD signal. At the same time, Nie et al. being inspired from Gao et al. took imaging at the next level.^53,76 They tried to travel the space between the cancer biomarker and the molecular cancer diagnosis and suggested that nanoparticles can be used to quantify a panel of the biomarkers because they are larger enough to conjugate with multiple ligands and enhanced affinity. Nie et al. demonstrated that there could be simultaneous staining of the four different biomarkers with expression profile which can’t be achieved through any of the conventional ways.

CONCLUSION:

Carbon dots are the fluorescent nanomaterials that have emerged recently providing an alternative to conventional toxic metal-based quantum dots. 2-15 nm is the size range of carbon dots, they are the fluorescence nanomaterials which is composed of carbon element. Carbon dot exhibits unique optical properties such as efficient fluorescence performance, high photostability, broad excitation spectra, and size-dependent emission wavelength. Their synthesis is quite simple as compared to the quantum dots, they have quite a high surface area for easy functionalization. These are highly soluble in water and show a great degree of bio-compatibleness.

CONFLICT OF INTEREST:

Conflict of interest declared none.

REFERENCES:

1. Alivisatos A. Perspectives on the physical chemistry of semiconductor nanocrystals. J Phys Chem 1996; 100:13226 – 39.

2. Suntherland A. Quantum dots as luminescent probes in biological systems. Curr Opin Solid State Mater Sci 2002; 6:36 – 370.

3. Henglein A. 1989. Small-particle research—physicochemical properties of extremely small colloidal metal and semiconductor particles. Chem. Rev. 89:1861– 73

4. Schmid G. 1992. Large clusters and colloids—metals in the embryonic state. Chem. Rev. 92:1709–27

5. Niemeyer CM. 2001. Nanoparticles, proteins, and nucleic acids: biotechnology meets materials science. Angew. Chem. Int. Ed. Engl. 40:4128–5811.

6. Alivisatos P. 2004. The use of nanocrystals in biological detection. Nat. Biotechnol. 22:47–52

7. Timely review article on the emergence of cancer nanotechnology and its clinical impact. 6. Ferrari M. 2005. Cancer nanotechnology: opportunities and challenges. Nat. Rev. Cancer 5:161–71

8. Srinivas PR, Barker P, Srivastava S. 2002. Nanotechnology in early detection of cancer. Lab. Invest. 82:657–62

9. Harisinghani MG, Barentsz J, Hahn PF, Deserno WM, Tabatabaei S, et al. 2003. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N. Engl. J. Med. 348:2491–99

10. Alivisatos AP. 1996. Semiconductor clusters, nanocrystals, and quantum dots. Science 271:933–37

11. Alivisatos AP, Gu WW, Larabell C. 2005. Quantum dots as cellular probes. Annu. Rev. Biomed. Eng. 7:55–76

12. Pinaud F, Michalet X, Bentolila LA, Tsay JM, Doose S, et al. 2006. Advances in fluorescence imaging with quantum dot bio-probes. Biomaterials 27:1679–8715.

13. Michalet X, Pinaud FF, Bentolila LA, Tsay JM, Doose S, et al. 2005. Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307:538–44

14. Gao XH, Yang LL, Petros JA, Marshal FF, Simons JW, Nie SM. 2005. In vivo molecular and cellular imaging with quantum dots.Curr. Opin. Biotechnol. 16:63– 72

15. Smith AM, Gao X, Nie S. 2004. Quantum dot nanocrystals for in vivo molecular and cellular imaging. Photochem. Photobiol. 80:377–85

16. Chan WCW, Maxwell DJ, Gao XH, Bailey RE, Han MY, Nie SM. 2002. Luminescent quantum dots for multiplexed biological detection and imaging. Curr. Opin. Biotechnol. 13:40–46

17. Hanahan D, Weinberg RA. 2000. The hallmarks of cancer. Cell 100:57–70

18. Hahn WC, Weinberg RA. 2002. Modelling the molecular circuitry of cancer. Nat. Rev. Cancer 2:331–41

19. Liotta L, Petricoin E. 2000. Molecular profiling of human cancer. Nat. Rev. Genet. 1:48–56

20. Menon U, Jacobs IJ. 2000. Recent developments in ovarian cancer screening. Curr. Opin. Obstet. Gynecol. 12:39–42

21. Bruchez, M., Jr, Moronne, M., Gin, P., Weiss, S. & Alivisatos, A.P. Semiconductor nanocrystals as fluorescent biological labels. Science 281, 2013–2015 (1998).

22. Chan, W.C.W. & Nie, S.M. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281, 2016–2018 (1998).

23. Mattoussi, H. et al. Self-assembly of CdSe-ZnS quantum dot bioconjugates using an engineered recombinant protein . J. Am. Chem. Soc. 122, 12142–12150 (2000).

24. Akerman, M.E., Chan, W.C.W., Laakkonen, P., Bhatia, S.N. & Ruoslahti, E. Nanocrystal targeting in vivo. Proc. Natl. Acad. Sci. USA 99, 12617–12621 (2002).

25. Dubertret, B. et al. In vivo imaging of QDs encapsulated in phospholipid micelles. Science 298, 1759–1762 (2002).

26. Wu, X.Y. et al. Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor QDs. Nat. Biotechnol. 21, 41–46 (2003).

27. Jaiswal, J.K., Mattoussi, H., Mauro, J.M. & Simon, S.M. Long-term multiple color imaging of live cells using quantum dot bioconjugates. Nat. Biotechnol. 21, 47–51 (2003).

28. Larson, D.R. et al. Water-soluble quantum dots for multiphoton fluorescence imaging in vivo. Science 300, 1434–1436 (2003).

29. Ishii, D. et al. Chaperonin-mediated stabilization and ATP-triggered release of semiconductor nanoparticles. Nature 423, 628–632 (2003).

30. Medintz, I.L. et al. Self-assembled nanoscale biosensors based on quantum dot FRET donors. Nat. Mater. 2, 630–639 (2003).

31. Dahan, M. et al. Diffusion dynamics of glycine receptors revealed by single–quantum dot tracking. Science 302, 442–445 (2003).

32. Rosenthal, S.J. et al. Targeting cell surface receptors with ligand-conjugated nanocrystals. J. Am. Chem. Soc.124, 4586–4594 (2002).

33. Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M, et al. 1999. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286:531–37

34. Ross DT, Scherf U, Eisen MB, Perou CM, Rees C, et al. 2000. Systematic variation in gene expression patterns in human cancer cell lines. Nat. Genet. 24:227–35

35. Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, et al. 2000. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403:503–11

36. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, et al. 2000. Molecular portraits of human breast tumours. Nature 406:747–52

37. Bittner M, Meitzer P, Chen Y, Jiang Y, Seftor E, et al. 2000. Molecular classifi- cation of cutaneous malignant melanoma by gene expression profiling. Nature 406:536–40

38. Dhanasekaran SM, Barrette TR, Ghosh D, Shah R, Varambally S, et al. 2001. Delineation of prognostic biomarkers in prostate cancer. Nature 412:822–26

39. Kuefer R, Varambally S, Zhou M, Lucas PC, Loeffler M, et al. 2002. α-Methyl acyl-CoA racemase: expression levels of this novel cancer biomarker depend on tumor differentiation. Am. J. Pathol. 161:841–48

40. Nelson WG, De Marzo AM, Isaacs WB. 2003. Mechanisms of disease: prostate cancer. N. Engl. J. Med. 349:366–81

41. Gonzalgo ML, Pavlovich CP, Lee SM, Nelson WG. 2003. Prostate cancer detection by GSTP1 methylation analysis of postbiopsy urine specimens. Clin. Cancer Res. 9:2673–77

42. Weinshilboum R, Wang LW. 2004. Pharmacogenomics: bench to bedside. Nat. Rev. Drug Discov. 3:739–48

43. Evans WE, Relling MV. 2004. Moving towards individualized medicine with pharmacogenomics. Nature 429:464–68 282

44. Michener CM, Ardekani AM, Petricoin EF, Liotta LA, Kohn EC. 2002. Genomics and proteomics: application of novel technology to early detection and prevention of cancer. Cancer Detect. Prev. 26:249–55

45. Srinivas PR, Verma M, Zhao Y, Srivastava S. 2002. Proteomics for cancer biomarker discovery. Clin. Chem. 48:1160–69

46. Niemeyer, C.M. Nanoparticles, proteins, and nucleic acids: biotechnology meets materials science. Angew. Chem. Int. Ed. Engl. 40, 4128–4158 (2001).

47. Alivisatos, A.P. Semiconductor clusters, nanocrystals, and quantum dots. Science 271, 933–937 (1996).

48. Han, M.Y., Gao, X.H., Su, J.Z. & Nie, S.M. Quantum dot-tagged microbeads for multiplexed optical coding of biomolecules. Nat. Biotechnol. 19, 631–635 (2001).

49. Gao, X.H. & Nie, S.M. Doping mesoporous materials with multicolor quantum dots. J. Phys. Chem. B. 107, 11575–11578 (2003).

50. Gao, X.H. & Nie, S.M. Quantum dot-encoded mesoporous beads with high brightness and uniformity: rapid readout using flow cytometry. Anal. Chem. 76, 2406–2410 (2004).

51. Kim SW, Zimmer JP, Ohnishi S, Tracy JB, Frangioni JV, Bawendi MG. 2005. Engineering InAsxP1-x/InP/ZnSe III-V alloyed core/shell quantum dots for the near-infrared. J. Am. Chem. Soc. 127:10526–32

52. Yu WW, Qu LH, Guo WZ, Peng XG. 2003. Experimental determination of the extinction coefficient of CdTe, CdSe, and CdS nanocrystals. Chem. Mater. 15:2854–60

53. Gao XH, Cui YY, Levenson RM, Chung LWK, Nie SM. 2004. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat. Biotechnol. 22:969–76

54. Matsumura Y, Maeda H. 1986. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 46:6387–92

55. Duncan R. 2003. The dawning era of polymer therapeutics. Nat. Rev. Drug Discov. 2:347–60.

56. Jain RK. 1999. Transport of molecules, particles, and cells in solid tumors. Annu. Rev. Biomed. Eng. 1:241–63

57. Jain RK. 2001. Delivery of molecular medicine to solid tumors: lessons from in vivo imaging of gene expression and function. J. Control Release 74:7–25

58. Savic, R., Luo, L.B., Eisenberg, A. & Maysinger, D. Micellar nanocontainers distribute to defined cytoplasmic organelles. Science 300, 615–618 (2003).

59. Allen, C., Maysinger, D. & Eisenberg, A. Nano-engineering block copolymer aggregates for drug delivery. Colloids Surf. B Biointerfaces 16, 3–27 (1999).

60. Ludwigs, S. et al. Self-assembly of functional nanostructures from ABC triblock copolymers. Nat. Mater. 2, 744–747 (2003).

61. Duncan, R. The dawning era of polymer therapeutics. Nat. Rev. Drug Discov. 2, 347–360 (2003).

62. Jain, R.K. Transport of molecules, particles, and cells in solid tumors. Ann. Rev. Biomed. Eng. 1, 241–263 (1999).

63. Jain, R.K. Delivery of molecular medicine to solid tumors: lessons from in vivo imaging of gene expression and function. J. Control. Release 74, 7–25 (2001).

64. Kircher MF, Weissleder R, Josephson L. 2004. A dual fluorochrome probe for imaging proteases. Bioconjug. Chem. 15:242–48

65. Schellenberger EA, Sosnovik D, Weissleder R, Josephson L. 2004. Magneto/ optical annexin V, a multimodal protein. Bioconjug. Chem. 15:1062–67

66. Wang DS, He JB, Rosenzweig N, Rosenzweig Z. 2004. Superparamagnetic Fe2O3 Beads-CdSe/ZnS quantum dots core-shell nanocomposite particles for cell separation. Nano Lett. 4:409–13

67. Gu H, Zheng R, Zhang X, Xu B. 2004. Facile one-pot synthesis of bifunctional heterodimers of nanoparticles: a conjugate of quantum dot and magnetic nanoparticles. J. Am. Chem. Soc. 126:5664–65

68. Reubi JC. In vitro identification of VIP receptors in human tumors: potential clinical implications. Ann N Y Acad Sci 1996;805:753 - 9.

69. Reubi JC. In vitro identification of vasoactive intestinal peptide receptors in human tumors: implications for tumor imaging. J Nucl Med 1995;36:1846 - 53.

70. Dagar S, Krishnadas A, Rubinstein I, Blend MJ, Onyuksel H. VIP grafted sterically stabilized liposomes for targeted imaging of breast cancer: in vivo studies. J Control Release 2003;91:123 - 33.

71. Gandon Y, Heautot JF, Brunet F, Guyader D, Deugnier Y, Carsin M. Superparamagnetic iron oxide: clinical time-response study. Eur J Radiol 1991;12:195 - 200.

72. Gupta AK, Berry C, Gupta M, Curtis A. Receptor-mediated targeting of magnetic nanoparticles using insulin as a surface ligand to prevent endocytosis. IEEE Trans Nanobioscience 2003;2:255 - 61.

73. Chang, S.S., Reuter, V.E., Heston, W.D.W. & Gaudin, P.B. Metastatic renal cell carcinoma neovasculature expresses prostate-specific membrane antigen. Urology 57, 801–805 (2001).

74. Schulke, N. et al. The homodimer of prostate-specific membrane antigen is a functional target for cancer therapy. Proc. Natl. Acad. Sci. USA 100, 12590–12595 (2003).

75. Bander, N.H. et al. Targeting metastatic prostate cancer with radiolabeled monoclonal antibody J591 to the extracellular domain of prostate specific membrane antigen. J. Urol. 170, 1717–1721 (2003).

76. Nie, Shuming et al. Nanotechnology Application in cancer. Annu. Rev. Biomed. Eng. 2007.9.257-88.

77. Gref R, Minamitake Y, Peracchia MT, Trubetskoy V, Torchilin V, Langer R. 1994. Biodegradable long-circulating polymeric nanospheres. Science 263:1600– 3.

Received on 24.08.2018 Accepted on 16.10.2018

Asian J. Pharm. Res. 2018; 8(4): 243-248.

DOI: 10.5958/2231-5691.2018.00042.4