期刊
SMALL
卷 16, 期 38, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202003309
关键词
biodegradation; cancer stem cells; cancer theranostics; drug resistance; mesoporous silica nanoparticles
类别
资金
- Department of Science and Technology (DST) Nano Mission, Government of India [SR/NM/NS-1152/2016]
- Department of Biotechnology (DBT), Government of India [BT/PR26670/NNT/28/1367/2017]
- CSIR Mission mode project, Nano Biosensor and Microfluidics for Healthcare [HCP-0012]
- SERB, Department of Science and Technology, Govt. of India [EMR/2017/000593-II]
- Science and Engineering Research Board, DST, Government of India [PDF/2016/001391, PDF/2017/000078]
- CSIR, Government of India [B-12612/2019, 0568/2018, 0589/2019]
The downsides of conventional cancer monotherapies are profound and enormously consequential, as drug-resistant cancer cells and cancer stem cells (CSC) are typically not eliminated. Here, a targeted theranostic nano vehicle (TTNV) is designed using manganese-doped mesoporous silica nanoparticle with an ideal surface area and pore volume for co-loading an optimized ratio of antineoplastic doxorubicin and a drug efflux inhibitor tariquidar. This strategically framed TTNV is chemically conjugated with folic acid and hyaluronic acid as a dual-targeting entity to promote folate receptor (FR) mediated cancer cells and CD44 mediated CSC uptake, respectively. Interestingly, surface-enhanced Raman spectroscopy is exploited to evaluate the molecular changes associated with therapeutic progression. Tumor microenvironment selective biodegradation and immunostimulatory potential of the MSN-Mn core are safeguarded with a chitosan coating which modulates the premature cargo release and accords biocompatibility. The superior antitumor response in FR-positive syngeneic and CSC-rich human xenograft murine models is associated with a tumor-targeted biodistribution, favorable pharmacokinetics, and an appealing bioelimination pattern of the TTNV with no palpable signs of toxicity. This dual drug-loaded nano vehicle offers a feasible approach for efficient cancer therapy by on demand cargo release in order to execute complete wipe-out of tumor reinitiating cancer stem cells.
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