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Successively triggered Rod-shaped protocells for enhanced tumor Chemo-Photothermal therapy
Wei Zhang1, Lu Chen1, Mingshu Cui1
1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Abstract:
Abundant existence of extracellular matrix biological hydrogels in solid tumors precludes most therapeutics to arrive at intracellular target sites, which is probably one of the threatened reasons of pancreatic ductal adenocarcinoma (PDAC) for public health. In this study, we designed a rod-shaped protocell nanoparticle loading with doxorubicin hydrochloride (Dox) and indocyanine green (ICG), denoted as Dox/ICG-RsPNs, for enhanced chemo-photothermal PDAC treatment. The enhanced therapeutic efficacy was achieved by successively enhancing penetration across matrix hydrogels, endocytosis, increasing local temperature under laser irradiation and hyperthermia-triggered Dox release to nucleus. We found that RsPNs with rod shape could easily penetrate across matrix hydrogel, exerting excellent tumor accumulation. Then RsPNs was internalized effectively by BxPC-3 cells via a caveolin-mediated endocytosis pathway. In addition, ICG endowed the Dox/ICG-RsPNs with photothermal effect and the photothermal conversion efficiency was calculated for 16.2%. Under irradiation, a great number of Dox transported to the nucleus via hyperthermia-induced release. Furthermore, we found that the relative tumor volume of Dox/ICG-RsPNs was merely 1.37 under irradiation at the end of pharmacodynamic studies, which was significantly lower than that of other groups. These findings will provide a promise on the rational design of drug delivery system for effective chemo-photothermal combination therapy to treat PDAC.
Insights
Rod-shaped nanoparticles loaded with doxorubicin and indocyanine green effectively penetrate pancreatic tumors. This chemo-photothermal therapy enhances drug delivery and significantly reduces tumor volume in pancreatic ductal adenocarcinoma (PDAC) treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Extracellular matrix hydrogels in solid tumors hinder therapeutic drug delivery.
- Pancreatic ductal adenocarcinoma (PDAC) poses a significant public health challenge due to treatment limitations.
Purpose of the Study:
- To design a novel nanoparticle for enhanced chemo-photothermal therapy in PDAC.
- To improve drug penetration, cellular uptake, and targeted drug release for PDAC treatment.
Main Methods:
- Development of rod-shaped protocell nanoparticles (RsPNs) loaded with doxorubicin hydrochloride (Dox) and indocyanine green (ICG).
- Evaluation of nanoparticle penetration through matrix hydrogels and cellular uptake via caveolin-mediated endocytosis.
- Assessment of photothermal effect and hyperthermia-triggered drug release under laser irradiation.
- Pharmacodynamic studies to evaluate tumor volume reduction.
Main Results:
- Rod-shaped RsPNs demonstrated enhanced penetration of matrix hydrogels and significant tumor accumulation.
- Dox/ICG-RsPNs were effectively internalized by BxPC-3 cells.
- Indocyanine green (ICG) provided a photothermal conversion efficiency of 16.2%, facilitating hyperthermia-induced Dox release to the nucleus.
- Significant reduction in relative tumor volume (1.37) was observed with Dox/ICG-RsPNs under irradiation compared to control groups.
Conclusions:
- The designed Dox/ICG-RsPNs show promise for overcoming extracellular matrix barriers in PDAC.
- This chemo-photothermal strategy offers an effective approach for targeted drug delivery and combination therapy in PDAC.
- Rational design of such drug delivery systems can significantly improve therapeutic outcomes for PDAC.
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