Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 28, Issue 50, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201806162
Keywords
enhanced permeability and retention; intra-abdominal metastases; intraperitoneal injection; nanocarrier; stimuli-responsive release
Categories
Funding
- Singapore National Research Foundation Investigatorship [NRF-NRFI2018-03]
- National Key R&D Program of China [2017YFA0205100]
- National Science Foundation of China [81702998, 81701766, 21628401]
- China Postdoctoral Science Foundation [2018M632006]
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Nanoparticle-based delivery systems (NDS) have impacted the field of cancer therapy on account of the enhanced permeability and retention (EPR) effect that promotes passive accumulation in tumors through the tumor vasculature after intravenous (IV) administration. However, transplanted tumor xenografts on animal models used to justify the feasibility of EPR effect are quite different from clinical tumors in many aspects, a fact that becomes an impediment for NDS to succeed clinical trials. Particularly, early-stage tumor metastases are usually nonvascularized and incapable of conforming the EPR effect after IV injection. Therefore, it is necessary to develop smart NDS to deliver drugs in an EPR-independent route. Herein, an NDS-based treatment approach for intra-abdominal metastases from ovarian carcinoma is reported. Instead of IV injection, intraperitoneal (IP) injection was employed to directly apply the NDS to the metastatic lesions. The NDS was tailor-made with targeting groups to actively target the tumor nidus and redox-responsive drug release to reduce systematic toxicity. Comparing with IV administration, the IP injected NDS could be enriched in metastatic tumor more efficiently, leading to superior therapeutic outcome in vivo. This study provides a successful protocol of EPR-independent NDS-based cancer treatment, which may facilitate the clinical translation of nanoparticle-based cancer therapeutics.
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