Self-assembly delivery system based on small-molecule camptothecin prodrug for treatment of colorectal carcinoma
Abstract
The aim of this study was to prepare small-molecule camptothecin (CPT) prodrugs and evaluate their effectiveness in colorectal carcinoma therapy. Prodrug nanoparticles (NPs) were physicochemically characterized and evaluated for their cytotoxicity in human colon cancer (HCT116) cell lines. The antitumor efficacy of the NPs was evaluated in HCT116 tumor-bearing mice. The prepared NPs exhibited high drug loading capacity (32% of CPT w/w) and also kept a high active lactone fraction of CPT (>85%) during circulation. The NPs were internalized into tumor cells efficiently compared with free drug and significantly enhanced the drug's therapeutic efficacy. The developed small-molecule CPT prodrug NPs could be a promising strategy in the clinical therapy of colorectal carcinoma.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. Polymeric nanoparticles with ROS-responsive prodrug and platinum nanozyme for enhanced chemophotodynamic therapy of colon cancer. Adv. Sci. (Weinh.) 7(20), 2001853 (2020).
- 2. Self-assembling nanoparticles of dually hydrophobic prodrugs constructed from camptothecin analogue for cancer therapy. Eur. J. Med. Chem. 200, 112365 (2020).
- 3. Transformative nanomedicine of an amphiphilic camptothecin prodrug for long circulation and high tumor uptake in cancer therapy. ACS Nano 11(9), 8838–8848 (2017). • Shows the strategy of transformative nanomedicine is promising for efficient drug delivery.
- 4. Novel polymeric micelles as enzyme-sensitive nuclear-targeted dual-functional drug delivery vehicles for enhanced 9-nitro-20(S)-camptothecin delivery and antitumor efficacy. Nanoscale 12(9), 5380–5396 (2020).
- 5. . A kinetic and mechanistic study of the hydrolysis of camptothecin and some analogues. J. Pharm. Sci. 81(7), 676–684 (1992).
- 6. Modification of the hydroxy lactone ring of camptothecin: inhibition of mammalian topoisomerase I and biological activity. J. Med. Chem. 32(3), 715–720 (1989).
- 7. . The structural basis of camptothecin interactions with human serum albumin: impact on drug stability. J. Med. Chem. 37(1), 40–46 (1994).
- 8. . Development of a highly active nanoliposomal irinotecan using a novel intraliposomal stabilization strategy. Cancer Res. 66(6), 3271–3277 (2006).
- 9. . PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. J. Am. Chem. Soc. 130(33), 10876–10877 (2008).
- 10. . An anticancer drug delivery system based on surfactant-templated mesoporous silica nanoparticles. Biomaterials 31(12), 3335–3346 (2010).
- 11. . Nanodiamonds as intracellular transporters of chemotherapeutic drug. Biomaterials 31(32), 8410–8418 (2010).
- 12. . Disulfide cross-linked phosphorylch-oline micelles for triggered release of camptothecin. Mol. Pharm. 10(7), 2684–2692 (2013).
- 13. . Dual stable nanomedicines prepared by cisplatin-crosslinked camptothecin prodrug micelles for effective drug delivery. ACS Appl. Mater. Interfaces 11(23), 20649–20659 (2019).
- 14. . Preclinical and clinical studies of NK012, an SN-38-incorporating polymeric micelles, which is designed based on EPR effect. Adv. Drug Deliv. Rev. 63(3), 184–192 (2011).
- 15. . Enhanced active liposomal loading of a poorly soluble ionizable drug using supersaturated drug solutions. J. Control. Release 162(2), 330–339 (2012).
- 16. . A mesoporous silica nanoparticle–PEI–fusogenic peptide system for siRNA delivery in cancer therapy. Biomaterials 34(4), 1391–1401 (2013).
- 17. Novel SN38 conjugate-forming nanoparticles as anticancer prodrug: in vitro and in vivo studies. J. Control. Release 166(2), 147–158 (2013).
- 18. . Prodrug and nanomedicine approaches for the delivery of the camptothecin analogue SN38. J. Control. Release 172(1), 48–61 (2013).
- 19. . The role of pH and ring-opening hydrolysis kinetics on liposomal release of topotecan. J. Control. Release 174, 88–97 (2014).
- 20. Reduction stimuli-responsive unimolecular polymeric prodrug based on amphiphilic dextran-framework for antitumor drug delivery. Carbohydr. Polym. 182, 235–244 (2018).
- 21. . Rational design of an amphiphilic chlorambucil prodrug realizing self-assembled micelles for efficient anticancer therapy. ACS Biomater. Sci. Eng. 4(3), 973–980 (2018).
- 22. Rational design of a new self-codelivery system from redox-sensitive camptothecin-cytarabine conjugate assembly for effectively synergistic anticancer therapy. Adv. Healthc. Mater. 6(24), 1700829 (2017).
- 23. Self-assembling nanowires of an amphiphilic camptothecin prodrug derived from homologous derivative conjugation. Chem. Commun. (Camb.) 52(98), 14145–14148 (2016).
- 24. Efficient click synthesis of a protonized and reduction-sensitive amphiphilic small-molecule prodrug containing camptothecin and gemcitabine for a drug self-delivery system. Mol. Pharm. 16(9), 3770–3779 (2019).
- 25. Prodrugs forming high drug loading multifunctional nanocapsules for intracellular cancer drug delivery. J. Am. Chem. Soc. 132(12), 4259–4265 (2010).
- 26. Supramolecular nanostructures formed by anticancer drug assembly. J. Am. Chem. Soc. 135(17), 2907–2910 (2013).
- 27. Combination of small molecule prodrug and nanodrug delivery: amphiphilic drug-drug conjugate for cancer therapy. J. Am. Chem. Soc. 136(33), 11748–11756 (2014).
- 28. . Carrier-free Janus nano-prodrug based on camptothecin and gemcitabine: reduction-triggered drug release and synergistic in vitro antiproliferative effect in multiple cancer cells. Int. J. Pharm. 550(1–2), 45–56 (2018).
- 29. Redox-sensitive lipophilic prodrugs: delivering unstable chemotherapeutant for improved cancer therapy. Drug Deliv. 26(1), 1068–1079 (2019).
- 30. Self-assembled redox dual-responsive prodrug-nanosystem formed by single thioether-bridged paclitaxel-fatty acid conjugate for cancer chemotherapy. Nano Lett. 16(9), 5401–5418 (2016). • Demonstrates that small-molecule prodrug nanosystem could be a promising strategy for efficient anticancer drug delivery.
- 31. Facile fabrication of tumor redox-sensitive nanoassemblies of small-molecule oleate prodrug as potent chemotherapeutic nanomedicine. Small 12(46), 6353–6362 (2016). •• Demonstrates that redox-responsive prodrug nanosystem exhibits multiple therapeutic advantages, including one-step facile fabrication, high drug loading efficiency (56% w/w), on-demand drug release responding to redox stimuli and favorable cellular uptake and biodistribution.
- 32. . A small molecule nanodrug consisting of amphiphilic targeting ligand-chemotherapy drug conjugate for targeted cancer therapy. J. Control. Release 230, 34–44 (2016).
- 33. Vitamin B6 tethered endosomal pH responsive lipid nanoparticles for triggered intracellular release of doxorubicin. ACS Appl. Mater. Interfaces 8(44), 30407–30421 (2016). •• Demonstrates that vitamin B6-coupled molecules are more easily internalized by tumor cells via vitamin B6 transporting membrane carrier (VTC).
- 34. . Endoplasmic reticulum targeting tumour selective photocytotoxic oxovanadium(IV) complexes having vitamin-B6 and acridinyl moieties. Dalton Trans. 45(2), 783–796 (2016). • Discusses how vitamin B6 has been reported to play an important protective role against various diseases and cancers via its antioxidation, antiangiogenesis and anti-inflammatory effects.
- 35. . Vitamin B6 regulates mRNA expression of peroxisome proliferator-activated receptor-γ target genes. Exp. Ther. Med. 2(3), 419–424 (2011).
- 36. The efficiency of membrane transport of vitamin B6 coupled to poly(ester amine) gene transporter and transfection in cancer cells. Biomaterials 34(14), 3716–3728 (2013).
- 37. Dynamic core crosslinked camptothecin prodrug micelles with reduction sensitivity and boronic acid-mediated enhanced endocytosis: an intelligent tumor-targeted delivery nanoplatform. Int. J. Pharm. 580, 119250 (2020).
- 38. . A versatile strategy to create an active tumor-targeted chemo-photothermal therapy nanoplatform: a case of an IR-780 derivative co-assembled with camptothecin prodrug. Acta Biomater. 84, 356–366 (2019).
- 39. . Dual sensitive and temporally controlled camptothecin prodrug liposomes codelivery of siRNA for high efficiency tumor therapy. Biomaterials 35(36), 9731–9745 (2014).
- 40. Targeted camptothecin delivery via silicon nanoparticles reduces breast cancer metastasis. Biomaterials 240, 119791 (2020). • Camptothecin (CPT)-loaded porous silicon nanoparticles (pSiNPs) showed significant therapeutic effect on breast cancer metastasis in vivo.
- 41. Enzyme-triggered transcytosis of dendrimer-drug conjugate for deep penetration into pancreatic tumors. ACS Nano 14(4), 4890–4904 (2020).
- 42. Reduction-sensitive fluorescence enhanced polymeric prodrug nanoparticles for combinational photothermal-chemotherapy. Biomaterials 163, 14–24 (2018).
- 43. Redox/pH dual-stimuli responsive camptothecin prodrug nanogels for “on-demand” drug delivery. J. Control. Release 296, 93–106 (2019).
- 44. Detailed identification of plasma proteins adsorbed on copolymer nanoparticles. Angew. Chem. Int. Ed. Engl. 46(30), 5754–5756 (2007).
- 45. Improving targeting of metal-phenolic capsules by the presence of protein coronas. ACS Appl. Mater. Interfaces 8(35), 22914–22922 (2016).