Advanced Analytical Techniques for Characterizing Nanoparticle-Drug Conjugates: Enhancing Cancer Therapy through Precision and Innovation
Abstract
Nanoparticle-based drug delivery systems represent a transformative approach in cancer therapy, offering enhanced delivery and efficacy of chemotherapeutic agents. These systems exploit the unique properties of nanoparticles, such as their small size, large surface area, and ability to be functionalized, to target cancer cells more effectively than conventional methods. The encapsulation or conjugation of drugs to nanoparticles can improve solubility, stability, and bioavailability, enabling controlled and sustained release at the tumor site, thereby minimizing side effects and enhancing the therapeutic index. This review provides a comprehensive overview of the key analytical techniques employed to characterize nanoparticle-drug conjugates, focusing on their physicochemical, biological, and pharmacokinetic properties. The review highlights the importance of these techniques in ensuring the efficacy and safety of nanoparticle-drug conjugates, discussing the limitations of current methods and the crucial need for standardization in the field. By examining a range of methods, from basic techniques like Dynamic Light Scattering (DLS) to advanced approaches such as Nuclear Magnetic Resonance (NMR) spectroscopy and single-particle tracking, this review aims to equip researchers with the knowledge necessary to accurately characterize these complex systems and optimize their use in cancer therapy.
Keywords:
Nanoparticle-drug conjugates, cancer therapy, drug delivery, characterization techniques, Dynamic Light Scattering (DLS), Nuclear Magnetic Resonance (NMR) spectroscopy
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References
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20. Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC. Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev. 2014;66:2-25.
21. Wicki A, Witzigmann D, Balasubramanian V, Huwyler J. Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications. J Control Release. 2015;200:138-157.
22. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2007;2(12):751-760.
23. Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2013;65(1):36-48.
24. Kakullamarri PR, Rao KLN (2017) Enhanced Bioavailability and Anticancer Activity of Vitamin Analogs. J BioequivAvailab 9: 439-441
25. Gao X, Cui Y, Levenson RM, Chung LW, Nie S. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol. 2004;22(8):969-976.
26. McNeil SE. Nanotechnology for the biologist. J Leukoc Biol. 2005;78(3):585-594.
27. Parveen S, Misra R, Sahoo SK. Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine. 2012;8(2):147-166.
28. Manda P, Popescu C, Juluri A, Janga K, Kakulamarri PR, Narishetty S, et al. Micronized Zaleplon Delivery via Orodispersible Film and Orodispersible Tablets. AAPS PharmSciTech. 2018 Jan 19;19(3):1358–66.
29. Byrne JD, Betancourt T, Brannon-Peppas L. Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev. 2008;60(15):1615-1626.
30. Davis ME, Chen ZG, Shin DM. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov. 2008;7(9):771-782.
31. Conner SD, Schmid SL. Regulated portals of entry into the cell. Nature. 2003;422(6927):37-44.
32. Tallam AK, Sahithi A, Nuli MV. Evaluation of antibacterial property of anthocyanin extracted from brassica oleracea against gram-positive and gram-negative bacteria by using erythromycin as a standard drug. Int J Indig Herb Drug [Internet]. 2023Feb.19 8(1):1.
33. Jain RK, Stylianopoulos T. Delivering Nano medicine to solid tumors. Nat Rev Clin Oncol. 2010;7(11):653-664.
34. Kakulamarri PR, Latha Alikatte K. Transdermal Iontophoresis of Non-Polar Drugs: A Mini Review. Journal of Pharmaceutics & Drug Delivery Research. 2016;5(3).
35. Wang AZ, Langer R, Farokhzad OC. Nanoparticle delivery of cancer drugs. Annu Rev Med. 2012;63:185-198.
36. Moghimi SM, Hunter AC, Murray JC. Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev. 2001;53(2):283-318.
37. Farokhzad OC, Langer R. Impact of nanotechnology on drug delivery. ACS Nano. 2009;3(1):16-20.
38. Lakshmi Narasimha Rao K, Praneeth Rao K. Development and Validation of a Stability-Indicating LC Method for Determination of Bexarotene in Softgel Dosage Formulation. Chromatographia. 2017 Jun 23;80(8):1211–24
39. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release. 2000;65(1-2):271-284.
40. Danhier F, Feron O, Préat V. To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release. 2010;148(2):135-146.
41. Rao Kakullamarri P, Tiyyagura P, Suresh Babu K. A Stable Formulation of a Non-Steroidal Anti-inflammatory Drug, Ibuprofen and an Antihistamine drug, Famotidine for a Combination Therapy. Journal of International Research in Medical and Pharmaceutical Sciences. 2023 Nov 1;18(2):38–50.
42. Brigger I, Dubernet C, Couvreur P. Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev. 2012;64(1):24-36.
43. Tallam, A. K., Alapati , S., & Nuli, M. V. (2023). A review on bioanalytical method development and validation of anticancer drugs by using lc/ms/ms and its applications on routine analysis. Journal of Integral Sciences, 6(1), 4-19. https://doi.org/10.37022/jis.v6i1.51
44. Tallam AK, Sahithi A, Nuli MV. A Review on Peptide-based Therapeutics For Combatting COVID-19. International Journal of Applied Pharmaceutical Sciences And Research. 2023 Apr 26;8(01):8-16.
2. Kumar, T. Anil, B. M. Gurupadayya, and MB Rahul Reddy. "Selective and validated spectrophotometric assay for microgram determination of ganciclovir with 1-fluoro-2, 4-dinitrobenzene and N-bromosuccinimide reagents." Journal of Applied Chemical Research 20.1 (2012): 14-27.
3. Wang AZ, Langer R, Farokhzad OC. Nanoparticle delivery of cancer drugs. Annu Rev Med. 2012;63:185-198.
4. Barenholz Y. Doxil®—the first FDA-approved nano-drug: Lessons learned. J Control Release. 2012;160(2):117-134.
5. Zhang L, Gu FX, Chan JM, Wang AZ, Langer RS, Farokhzad OC. Nanoparticles in medicine: therapeutic applications and developments. Clin Pharmacol Ther. 2008;83(5):761-769.
6. Anil Kumar. T. “Development and validation of RP-LC-UV method for determination of ursodeoxycholic acid in drug substance and drug product”. Journal of Global Trends in Pharmaceutical Sciences, 2016; 7(3): 3429- 3435.
7. Anil Kumar T,Kausal Kishore Chandrul. “Development and Validation of RP-LC-UV Method for Determination of Ursodeoxycholic Acid in Drug Substance and Drug Product”. Journal of Global Trends in Pharmaceutical Sciences, 2018; 9(3): 5808- 5815.
8. Kumar, T. Anil, et al. "Selective and validated spectrophotometric method for determination of acyclovir and valacyclovir using N-Bromosuccinimide." Journal of Pharmacy Research 4.1 (2011): 24-27.
9. Kumar, T. Anil, B. M. Gurupadayya, and M. B. Reddy. "Selective and validated spectrophotometric methods for determination of ganciclovir with PDAB and Folin’s reagents." (2012).
10. Gradishar WJ, Tjulandin S, Davidson N, et al. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil–based paclitaxel in women with breast cancer. J Clin Oncol. 2005;23(31):7794-7803.
11. O’Brien ME, Wigler N, Inbar M, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX™/Doxil®) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004;15(3):440-449.
12. Papinaboina Venkata Rao, Chinnakadoori Sanjeeva Reddy, Ravi Kumar Marram, DantuDurga Rao, Simultaneous Determination Of Omeprazole And Domperidone In Capsules And In Vitro Dissolution Studies By Using Stability Indicating UPLC, Journal of liquid chromatography & related technologies, 2012, 35 (16), 2322-2332.
13. Kumar, T. Anil, et al. "Selective and Validated Spectrophotometric Methods for Determination of Acyclovir and Ganciclovirwith 2, 4 DNP as Reagent." Journal of Applied Chemical Research 6.1 (2012): 14-24.
14. Niroja Vadagam, Sharath Babu Haridasyam, MuvvalaVenkatanarayana, Narasimha S. Lakka, Sanjeeva R. Chinnakadoori, Separation and quantitative estimation of stereo-selective enantiomers of montelukast in pharmaceutical drug substance and tablets dosage forms by using stability-indicating normal phase-HPLC method, Chirality, 2023, 35(12), 952-965.
15. Niroja Vadagam, Sharath Babu Haridasyam, MuvvalaVenkatanarayana, Narasimha S Lakka, Sanjeeva R Chinnakadoori, Separation and quantitation of valacyclovir enantiomers using stability-indicating chiral liquid chromatography method with a chiral stationary phase of amylose tris-(3,5-dimethyl phenyl carbamate), Separation Science Plus, 2023, 6(12), 2300145.
16. Narasimha S Lakka, Chandrasekar Kuppan, Niroja Vadagam, Poornima Ravinathan, KalyaniChepuri, Sanjeeva R Chinnakadoori, Molecular docking, in-vitro anticancer evaluation and ADME profiling of 7-Oxo Midostaurin, Journal of Molecular Structure, 2023, 1293, 136159.
17. Niroja Vadagam, Sharath Babu Haridasyam, MuvvalaVenkatanarayana, Narasimha S Lakka, Sanjeeva R Chinnakadoori, Separation and simultaneous estimation of enantiomers and Diastereomers of muscarinic receptor antagonist Solifenacin using stability-indicating Normal-phase HPLC technique with chiral stationary phase amylose tris-(3,5-dimethylphenylcarbamate), Chirality, 2024, 36(2), e23632.
18. Mohan Pasham, Sharath Babu Haridasyam, Niroja Vadagam, NVVD Praveen Boppy, Sanjeeva R Chinnakadoori, Narasimha S Lakka, Separation and quantification of organic-related impurities of betaadrenergic receptor blocking agent propranolol in pharmaceutical solid dosage forms: Impurity profiling using stability-indicating HPLC method, 2024, 7(1), 2300159.
19. N. V. V. D. Praveen Boppy, Sharath Babu Haridasyam, Niroja Vadagam, MuvvalaVenkatanarayana, Sanjeeva R. Chinnakadoori, Narasimha S. Lakka, Separation and quantification of organicrelated impurities of anti-histamine drug hydroxyzine in pharmaceutical dosage forms using stability-indicating high-performance liquid chromatography, liquid chromatography-mass spectrometry, and high-resolution mass spectrometry techniques, Separation Science Plus, 2024, 2300157.
20. Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC. Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev. 2014;66:2-25.
21. Wicki A, Witzigmann D, Balasubramanian V, Huwyler J. Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications. J Control Release. 2015;200:138-157.
22. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2007;2(12):751-760.
23. Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2013;65(1):36-48.
24. Kakullamarri PR, Rao KLN (2017) Enhanced Bioavailability and Anticancer Activity of Vitamin Analogs. J BioequivAvailab 9: 439-441
25. Gao X, Cui Y, Levenson RM, Chung LW, Nie S. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol. 2004;22(8):969-976.
26. McNeil SE. Nanotechnology for the biologist. J Leukoc Biol. 2005;78(3):585-594.
27. Parveen S, Misra R, Sahoo SK. Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine. 2012;8(2):147-166.
28. Manda P, Popescu C, Juluri A, Janga K, Kakulamarri PR, Narishetty S, et al. Micronized Zaleplon Delivery via Orodispersible Film and Orodispersible Tablets. AAPS PharmSciTech. 2018 Jan 19;19(3):1358–66.
29. Byrne JD, Betancourt T, Brannon-Peppas L. Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev. 2008;60(15):1615-1626.
30. Davis ME, Chen ZG, Shin DM. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov. 2008;7(9):771-782.
31. Conner SD, Schmid SL. Regulated portals of entry into the cell. Nature. 2003;422(6927):37-44.
32. Tallam AK, Sahithi A, Nuli MV. Evaluation of antibacterial property of anthocyanin extracted from brassica oleracea against gram-positive and gram-negative bacteria by using erythromycin as a standard drug. Int J Indig Herb Drug [Internet]. 2023Feb.19 8(1):1.
33. Jain RK, Stylianopoulos T. Delivering Nano medicine to solid tumors. Nat Rev Clin Oncol. 2010;7(11):653-664.
34. Kakulamarri PR, Latha Alikatte K. Transdermal Iontophoresis of Non-Polar Drugs: A Mini Review. Journal of Pharmaceutics & Drug Delivery Research. 2016;5(3).
35. Wang AZ, Langer R, Farokhzad OC. Nanoparticle delivery of cancer drugs. Annu Rev Med. 2012;63:185-198.
36. Moghimi SM, Hunter AC, Murray JC. Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev. 2001;53(2):283-318.
37. Farokhzad OC, Langer R. Impact of nanotechnology on drug delivery. ACS Nano. 2009;3(1):16-20.
38. Lakshmi Narasimha Rao K, Praneeth Rao K. Development and Validation of a Stability-Indicating LC Method for Determination of Bexarotene in Softgel Dosage Formulation. Chromatographia. 2017 Jun 23;80(8):1211–24
39. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release. 2000;65(1-2):271-284.
40. Danhier F, Feron O, Préat V. To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release. 2010;148(2):135-146.
41. Rao Kakullamarri P, Tiyyagura P, Suresh Babu K. A Stable Formulation of a Non-Steroidal Anti-inflammatory Drug, Ibuprofen and an Antihistamine drug, Famotidine for a Combination Therapy. Journal of International Research in Medical and Pharmaceutical Sciences. 2023 Nov 1;18(2):38–50.
42. Brigger I, Dubernet C, Couvreur P. Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev. 2012;64(1):24-36.
43. Tallam, A. K., Alapati , S., & Nuli, M. V. (2023). A review on bioanalytical method development and validation of anticancer drugs by using lc/ms/ms and its applications on routine analysis. Journal of Integral Sciences, 6(1), 4-19. https://doi.org/10.37022/jis.v6i1.51
44. Tallam AK, Sahithi A, Nuli MV. A Review on Peptide-based Therapeutics For Combatting COVID-19. International Journal of Applied Pharmaceutical Sciences And Research. 2023 Apr 26;8(01):8-16.
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10-08-2024
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Bhuma SR, Potti S. Advanced Analytical Techniques for Characterizing Nanoparticle-Drug Conjugates: Enhancing Cancer Therapy through Precision and Innovation. World Journal of Current Med and Pharm Research [Internet]. 2024Aug.10 [cited 2025Apr.26];6(2):68-5. Available from: https://wjcmpr.com/index.php/journal/article/view/338
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