Journal
NANOTECHNOLOGY
Volume 32, Issue 8, Pages -Publisher
IOP PUBLISHING LTD
DOI: 10.1088/1361-6528/abcacb
Keywords
silver nanoparticles; combination therapy; tumor targeting; anti-cancer activity; drug nanocrystals; multi-functionalization
Funding
- Dalian Science and Technology Innovation Fund [2018J11CY028]
- Key Projects of Liaoning Natural Science Foundation Program [20180540130]
- Guangdong Basic and Applied Basic Research Foundation [2019A1515010630]
- Dalian Highlevel Personnel of Innovation Support Program [2018RQ41]
- General Program of Natural Science Foundation of Liaoning [20180550428]
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The study demonstrated the potential advantages of NR1/AgNP-decorated PTX nanocrystals in enhancing chemotherapy, improving anti-cancer activity, and inhibiting cancer cell migration, while achieving a balance between good selectivity and biocompatibility.
For chemotherapeutic drugs, precise tumor-targeting and high anti-cancer efficiency is equally important in order to enhance chemotherapy and reverse drug resistance. The combination of multifunctional agents to achieve synergy should be a promising strategy. In our study, we have successfully developed novel multifunctionalized drug nanocrystals to realize co-delivery of the organic drug Paclitaxel (PTX), inorganic silver nanoparticles (AgNPs) and a tumor targeting agent. To be specific, PTX nanocrystals were first prepared as a template, then coated with polydopamine (PDA). The PDA layer was utilized as the connection bridge to produce and deposit AgNPs in situ, and provide sites for tumor-targeting peptide NR1 (RGDARF) grafting. As a result, these NR1/AgNP-decorated drug nanocrystals exhibited dramatically improved cellular uptake efficiency, in vitro anti-cancer activity and an anti-migratory effect against a variety of cancer cells, which was attributable to the synergistic, or at least additive, effect of the AgNPs and PTX, enhanced cellular uptake efficiency through NR1-receptor interaction, pH-responsive drug release and the nanoscaled nature. In particular, high anti-cancer activity and low side effects from these NR1/AgNP-decorated PTX nanocrystals were well balanced in terms of good selectivity and biocompatibility. Moreover, these novel drug nanocrystals displayed strong apoptotic-inducing potency, resulting in cell membrane lysis, nuclear damage, mitochondria dysfunction, excessive ROS release and double-stranded DNA breakage. The potential acting mechanism and molecular basis of these novel drug nanocrystals is relevant to the regulation of mitochondria-mediated apoptosis with a greater Bax-to-Bcl-2 ratio and the activation of pro-apoptotic P53 and caspase 3.
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