Reductively-sheddable cationic nanocarriers for dual chemotherapy and gene therapy with enhanced release
Source abstract
Abstract
The development of a versatile strategy to synthesize cationic nanocarriers capable of co-delivery and enhanced release of drugs and oligonucleotides is promising for synergic dual chemotherapy and gene therapy. Herein, we report a novel cationic amphiphilic diblock copolymer having a single reduction-responsive disulfide linkage at a junction between a FDA-approved polylactide (PLA) block and a cationic methacrylate block (C-ssABP). The amphiphilic design of the C-ssABP enables the formation of cationic micellar aggregates possessing hydrophobic PLA cores, encapsulating anticancer drugs; cationic coronas, ensuring complementary complexation with negatively-charged oligonucleotides through electrostatic interactions; and disulfides at interfaces, leading to enhanced release of both encapsulated drugs and complexed oligonucleotides. The reduction-responsive intracellular trafficking results from flow cytometry, confocal laser scanning microscopy, and cell viability, as well as in vitro gene transfection assay suggest that C-ssABP offers versatility as an effective nanocarrier platform for dual chemotherapy and gene therapy.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: RNA Interference and Gene Delivery · Nanoparticle-Based Drug Delivery · Graphene and Nanomaterials Applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (60)
Show source-provided references
1. Block copolymer micelles for delivery of cancer therapy: transport at the whole body, tissue and cellular levels10.1016/j.jconrel.2009.04.010 ↗
2. Nanostructured devices based on block copolymer assemblies for drug delivery: designing structures for enhanced drug function10.1007/12_025 ↗
3. Engineering of amphiphilic block copolymers for polymeric micellar drug and gene delivery10.1016/j.jconrel.2011.04.028 ↗
4. Supramolecular assemblies of block copolymers in aqueous media as nanocontainers relevant to biological applications10.1016/j.progpolymsci.2006.09.004 ↗
5. Nano-engineering block copolymer aggregates for drug delivery10.1016/S0927-7765(99)00058-2 ↗
6. Living ring-opening polymerizations of heterocyclic monomers10.1016/j.progpolymsci.2007.01.002 ↗
7. Polylactic acid technology10.1002/1521-4095(200012)12:23<1841::AID-ADMA1841>3.0.CO;2-E ↗
8. Biodegradable polymeric nanoparticles based drug delivery systems10.1016/j.colsurfb.2009.09.001 ↗
9. New design of thiol-responsive degradable polylactide-based block copolymer micelles10.1002/marc.201200532 ↗
10. Biodegradable block copolymer micelles with thiol-responsive sheddable coronas10.1021/bm2011032 ↗
11. Functional poly(ɛ-caprolactone)s via copolymerization of ɛ-caprolactone and pyridyl disulfide-containing cyclic carbonate: controlled synthesis and facile access to reduction-sensitive biodegradable graft copolymer micelles10.1021/ma302499a ↗
12. Glutathione-triggered disassembly of dual disulfide located degradable nanocarriers of polylactide-based block copolymers for rapid drug release10.1021/bm5008508 ↗
13. (PLA)-based amphiphilic block copolymers: synthesis, self-assembly, and biomedical applications10.1039/c0sm01539c ↗
14. The microclimate pH in poly(d,l-lactide-co-hydroxymethyl glycolide) microspheres during biodegradation10.1016/j.biomaterials.2012.06.013 ↗
15. Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo10.1073/pnas.0601755103 ↗
16. In vivo evaluation of polymeric micellar paclitaxel formulation: toxicity and efficacy10.1016/S0168-3659(01)00275-9 ↗
17. Nanoparticles of poly(d,l-lactide)/methoxy poly(ethylene glycol)–poly(d,l-lactide) blends for controlled release of paclitaxel10.1002/jbm.a.30684 ↗
18. Hemoglobin conjugated micelles based on triblock biodegradable polymers as artificial oxygen carriers10.1016/j.biomaterials.2009.05.082 ↗
19. Multifunctional magneto-polymeric nanohybrids for targeted detection and synergistic therapeutic effects on breast cancer10.1002/anie.200703554 ↗
20. Nanoparticles for drug delivery prepared from amphiphilic PLGA zwitterionic block copolymers with sharp contrast in polarity between two blocks10.1002/anie.200907079 ↗
21. Synthesis, characterization, and molecular recognition of sugar-functionalized nanoparticles prepared by a combination of ROP ATRP, and click chemistry10.1002/pola.24105 ↗
22. Synthesis, characterization and preliminary biological evaluation of P(HPMA)-b-P(LLA) copolymers: a new type of functional biocompatible block copolymer10.1002/marc.201000090 ↗
23. Poly(lactide)-block-poly(HEMA) block copolymers: an orthogonal one-pot combination of ROP and ATRP, using a bifunctional initiator10.1021/ma900894d ↗
24. Thermo and pH dual-responsive nanoparticles for anti-cancer drug delivery10.1002/adma.200601817 ↗
25. Dual stimuli-dual response nanoassemblies prepared from a simple homopolymer10.1021/mz400515s ↗
26. Functionalizable amine-based polymer nanoparticles10.1021/mz4004248 ↗
27. Improving the oral delivery efficiency of anticancer drugs by chitosan coated polycaprolactone-grafted hyaluronic acid nanoparticles10.1039/C4TB00273C ↗
28. Biomaterials to gene delivery10.1016/j.jconrel.2011.03.023 ↗
29. Nonviral vectors for gene delivery10.1021/cr800409e ↗
30. Endosomal escape pathways for non-viral nucleic acid delivery systems10.5772/46006 ↗
31. Peptide- and polymer-based delivery of therapeutic RNA10.1039/B916053A ↗
32. Recent advances in nonviral vectors for gene delivery10.1021/ar200151m ↗
33. PDMAEMA based gene delivery materials10.1016/S1369-7021(12)70165-7 ↗
34. Synthesis of folate-functionalized RAFT polymers for targeted siRNA delivery10.1021/bm200485b ↗
35. Cationic amphiphilic star and linear block copolymers: synthesis, self-assembly, and in vitro gene transfection10.1021/bm2006906 ↗
36. Influence of nano-carrier architecture on in vitro siRNA delivery performance and in vivo biodistribution: polyplexes vs. micelleplexes10.1021/nn102540y ↗
37. Bioreducible polymers for gene silencing and delivery10.1021/ar200248u ↗
38. Bioreducible hyperbranched poly(amido amine)s for gene delivery10.1021/bm900724c ↗
39. Reducible poly(amido ethylenimine) directed to enhance RNA interference10.1016/j.biomaterials.2006.12.019 ↗
40. Novel bioreducible poly(amido amine)s for highly efficient gene delivery10.1021/bc060200l ↗
41. Rational design of smart supramolecular assemblies for gene delivery: chemical challenges in the creation of artificial viruses10.1039/C1CS15258K ↗
42. PEG-detachable polyplex micelles based on disulfide-linked block catiomers as bioresponsive nonviral gene vectors10.1021/ja800336v ↗
43. Reducible DNA nanoparticles enhance in vitro gene transfer via an extracellular mechanism10.1016/j.jconrel.2010.04.031 ↗
44. Synthesis and thiol-responsive degradation of polylactide-based block copolymers having disulfide junctions using ATRP and ROP10.1002/pola.26335 ↗
45. Poly(dl-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate): synthesis, characterization, micellization behavior in aqueous solutions, and encapsulation of the hydrophobic drug dipyridamole10.1021/bm901151g ↗
46. Amphiphilic poly(d- or l-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate) block copolymers: controlled synthesis, characterization, and stereocomplex formation10.1021/bm801515c ↗
47. Synthesis and thermal properties of linear amphiphilic diblock copolymers of l-lactide and 2-dimethylaminoethyl methacrylate10.1021/ma200449e ↗
48. Polymeric micelles with pendant dicarboxylato chelating ligands prepared via a Michael addition for cis-platinum drug delivery10.1021/ma2016503 ↗
49. Bioreducible micelles self-assembled from amphiphilic hyperbranched multiarm copolymer for glutathione-mediated intracellular drug delivery10.1021/bm200275j ↗
50. Biodegradable micelles with sheddable poly(ethylene glycol) shells for triggered intracellular release of doxorubicin10.1016/j.biomaterials.2009.07.051 ↗
51. Shell-sheddable micelles based on dextran-ss-poly(ɛ-caprolactone) diblock copolymer for efficient intracellular release of doxorubicin10.1021/bm1001069 ↗
52. Shell-sheddable micelles based on star-shaped poly(ɛ-caprolactone)-SS-poly(ethyl glycol) copolymer for intracellular drug release10.1039/c1sm05020f ↗
53. Redox-responsive hyperbranched poly(amido amine)s with tertiary amino cores for gene delivery10.1021/bm400460r ↗
54. Assessment of cholesterol-derived ionic copolymers as potential vectors for gene delivery10.1021/bm4013088 ↗
55. Folic acid modified cationic γ-cyclodextrin-oligoethylenimine star polymer with bioreducible disulfide linker for efficient targeted gene delivery10.1021/bm301718f ↗
56. Intracellular drug delivery nanocarriers of glutathione-responsive degradable block copolymers having pendant disulfide linkages10.1021/bm4004805 ↗
57. Reduction-responsive disassemblable core-cross-linked micelles based on poly(ethylene glycol)-b-poly(N-2-hydroxypropyl methacrylamide)-lipoic acid conjugates for triggered intracellular anticancer drug release10.1021/bm3006819 ↗
58. Polyplexes based on cationic polymers with strong nucleic acid binding properties10.1016/j.ejps.2011.09.002 ↗
59. Galactosylated ternary DNA/polyphosphoramidate nanoparticles mediate high gene transfection efficiency in hepatocytes10.1016/j.jconrel.2004.10.024 ↗
60. Self-assembled oligopeptide nanostructures for co-delivery of drug and gene with synergistic therapeutic effect10.1016/j.biomaterials.2009.03.006 ↗