Journal
NANO LETTERS
Volume 19, Issue 11, Pages 8010-8020Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.9b03211
Keywords
Transcytosis; tumor penetration; upconversion nanoparticles; photodynamic therapy
Categories
Funding
- National Science Foundation of China [31671027, 31671004, 81871502]
- National Key Research and Development Program of China [2017YFC1103900]
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The diffusion of nanomedicines used to treat tumors is severely hindered by the microenvironment, which is a challenge that has emerged as a bottleneck for the effective outcome of nanotherapies. Classical strategies for enhancing tumor penetration rely on passive movement in the extracellular matrix (ECM). Here, we demonstrate that nanomedicine also penetrates tumor lesions via an active trans-cell transportation process. This process was discovered by directly observing the movement of nanoparticles between cells, evaluating the intracellular trafficking pathway of nanoparticles via Rab protein labeling, comparing endocytosis-exocytosis between nanoparticles administered with inhibitors, and correlating the transcytosis process with the micro-CT distribution of nanomedicines. We also demonstrated that enhanced tumor penetration promotes the therapeutic efficacy of a photodynamic therapeutic nanomedicine. Our research thus suggests that transcytosis could be an important positive factor for designing cancer nanomedicines.
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