Subtherapeutic Photodynamic Treatment Facilitates Tumor Nanomedicine Delivery and Overcomes Desmoplasia

Marta Overchuk; Kara M. Harmatys; Shrey Sindhwani; Maneesha A. Rajora; Adam Koebel; Danielle M. Charron; Abdullah M. Syed; Juan Chen; Martin G. Pomper; Brian C. Wilson; Warren C.W. Chan; Gang Zheng

doi:10.1021/acs.nanolett.0c03731

Subtherapeutic Photodynamic Treatment Facilitates Tumor Nanomedicine Delivery and Overcomes Desmoplasia

Marta Overchuk, Kara M. Harmatys, Shrey Sindhwani, Maneesha A. Rajora, Adam Koebel, Danielle M. Charron, Abdullah M. Syed, Juan Chen, Martin G. Pomper, Brian C. Wilson, Warren C.W. Chan, Gang Zheng

School of Medicine

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Limited tumor nanoparticle accumulation remains one of the main challenges in cancer nanomedicine. Here, we demonstrate that subtherapeutic photodynamic priming (PDP) enhances the accumulation of nanoparticles in subcutaneous murine prostate tumors ∼3-5-times without inducing cell death, vascular destruction, or tumor growth delay. We also found that PDP resulted in an ∼2-times decrease in tumor collagen content as well as a significant reduction of extracellular matrix density in the subendothelial zone. Enhanced nanoparticle accumulation combined with the reduced extravascular barriers improved therapeutic efficacy in the absence of off-target toxicity, wherein 5 mg/kg of Doxil with PDP was equally effective in delaying tumor growth as 15 mg/kg of Doxil. Overall, this study demonstrates the potential of PDP to enhance tumor nanomedicine accumulation and alleviate tumor desmoplasia without causing cell death or vascular destruction, highlighting the utility of PDP as a minimally invasive priming strategy that can improve therapeutic outcomes in desmoplastic tumors.

Original language	English (US)
Pages (from-to)	344-352
Number of pages	9
Journal	Nano Letters
Volume	21
Issue number	1
DOIs	https://doi.org/10.1021/acs.nanolett.0c03731
State	Published - Jan 13 2021

Keywords

PSMA
extracellular matrix
nanomedicine
photodynamic therapy
prostate cancer

ASJC Scopus subject areas

Condensed Matter Physics
Mechanical Engineering
Bioengineering
General Chemistry
General Materials Science

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10.1021/acs.nanolett.0c03731

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@article{4c05cff2dce6432a91a898f02e1b2f78,

title = "Subtherapeutic Photodynamic Treatment Facilitates Tumor Nanomedicine Delivery and Overcomes Desmoplasia",

abstract = "Limited tumor nanoparticle accumulation remains one of the main challenges in cancer nanomedicine. Here, we demonstrate that subtherapeutic photodynamic priming (PDP) enhances the accumulation of nanoparticles in subcutaneous murine prostate tumors ∼3-5-times without inducing cell death, vascular destruction, or tumor growth delay. We also found that PDP resulted in an ∼2-times decrease in tumor collagen content as well as a significant reduction of extracellular matrix density in the subendothelial zone. Enhanced nanoparticle accumulation combined with the reduced extravascular barriers improved therapeutic efficacy in the absence of off-target toxicity, wherein 5 mg/kg of Doxil with PDP was equally effective in delaying tumor growth as 15 mg/kg of Doxil. Overall, this study demonstrates the potential of PDP to enhance tumor nanomedicine accumulation and alleviate tumor desmoplasia without causing cell death or vascular destruction, highlighting the utility of PDP as a minimally invasive priming strategy that can improve therapeutic outcomes in desmoplastic tumors.",

keywords = "PSMA, extracellular matrix, nanomedicine, photodynamic therapy, prostate cancer",

author = "Marta Overchuk and Harmatys, {Kara M.} and Shrey Sindhwani and Rajora, {Maneesha A.} and Adam Koebel and Charron, {Danielle M.} and Syed, {Abdullah M.} and Juan Chen and Pomper, {Martin G.} and Wilson, {Brian C.} and Chan, {Warren C.W.} and Gang Zheng",

note = "Funding Information: The authors would like to acknowledge Mark Zheng, Maartje Damen, and Dr. Miffy Cheng for their assistance with animal experiments. The authors also thank Deborah Scollard, Teesha Komal, and Dr. Manuela Ventura for technical assistance with imaging experiments. Additionally, the authors acknowledge members of STTARR Pathology Core Feryal Sarraf and Napoleon Law and Dr. Vivian Bradaschia from The Centre for Phenogenomics for their pathology services as well as Dr. Ali Darbandi at SickKids Hospital (Toronto) for help in preparing tissue grids for TEM. This study was funded by the Terry Fox Research Institute (PPG#1075), the Canadian Institute of Health Research (Foundation Grant #154326), the Vanier Canada Graduate Scholarship, the Canada Foundation for Innovation (no. 21765), the Natural Sciences and Engineering Research Council of Canada (no. 386613), the Canada Research Chair Programs, the Nanomedicine Innovation Network, and the Princess Margaret Cancer Foundation. Publisher Copyright: {\textcopyright} ",

year = "2021",

month = jan,

day = "13",

doi = "10.1021/acs.nanolett.0c03731",

language = "English (US)",

volume = "21",

pages = "344--352",

journal = "Nano Letters",

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TY - JOUR

T1 - Subtherapeutic Photodynamic Treatment Facilitates Tumor Nanomedicine Delivery and Overcomes Desmoplasia

AU - Overchuk, Marta

AU - Harmatys, Kara M.

AU - Sindhwani, Shrey

AU - Rajora, Maneesha A.

AU - Koebel, Adam

AU - Charron, Danielle M.

AU - Syed, Abdullah M.

AU - Chen, Juan

AU - Pomper, Martin G.

AU - Wilson, Brian C.

AU - Chan, Warren C.W.

AU - Zheng, Gang

N1 - Funding Information: The authors would like to acknowledge Mark Zheng, Maartje Damen, and Dr. Miffy Cheng for their assistance with animal experiments. The authors also thank Deborah Scollard, Teesha Komal, and Dr. Manuela Ventura for technical assistance with imaging experiments. Additionally, the authors acknowledge members of STTARR Pathology Core Feryal Sarraf and Napoleon Law and Dr. Vivian Bradaschia from The Centre for Phenogenomics for their pathology services as well as Dr. Ali Darbandi at SickKids Hospital (Toronto) for help in preparing tissue grids for TEM. This study was funded by the Terry Fox Research Institute (PPG#1075), the Canadian Institute of Health Research (Foundation Grant #154326), the Vanier Canada Graduate Scholarship, the Canada Foundation for Innovation (no. 21765), the Natural Sciences and Engineering Research Council of Canada (no. 386613), the Canada Research Chair Programs, the Nanomedicine Innovation Network, and the Princess Margaret Cancer Foundation. Publisher Copyright: ©

PY - 2021/1/13

Y1 - 2021/1/13

N2 - Limited tumor nanoparticle accumulation remains one of the main challenges in cancer nanomedicine. Here, we demonstrate that subtherapeutic photodynamic priming (PDP) enhances the accumulation of nanoparticles in subcutaneous murine prostate tumors ∼3-5-times without inducing cell death, vascular destruction, or tumor growth delay. We also found that PDP resulted in an ∼2-times decrease in tumor collagen content as well as a significant reduction of extracellular matrix density in the subendothelial zone. Enhanced nanoparticle accumulation combined with the reduced extravascular barriers improved therapeutic efficacy in the absence of off-target toxicity, wherein 5 mg/kg of Doxil with PDP was equally effective in delaying tumor growth as 15 mg/kg of Doxil. Overall, this study demonstrates the potential of PDP to enhance tumor nanomedicine accumulation and alleviate tumor desmoplasia without causing cell death or vascular destruction, highlighting the utility of PDP as a minimally invasive priming strategy that can improve therapeutic outcomes in desmoplastic tumors.

AB - Limited tumor nanoparticle accumulation remains one of the main challenges in cancer nanomedicine. Here, we demonstrate that subtherapeutic photodynamic priming (PDP) enhances the accumulation of nanoparticles in subcutaneous murine prostate tumors ∼3-5-times without inducing cell death, vascular destruction, or tumor growth delay. We also found that PDP resulted in an ∼2-times decrease in tumor collagen content as well as a significant reduction of extracellular matrix density in the subendothelial zone. Enhanced nanoparticle accumulation combined with the reduced extravascular barriers improved therapeutic efficacy in the absence of off-target toxicity, wherein 5 mg/kg of Doxil with PDP was equally effective in delaying tumor growth as 15 mg/kg of Doxil. Overall, this study demonstrates the potential of PDP to enhance tumor nanomedicine accumulation and alleviate tumor desmoplasia without causing cell death or vascular destruction, highlighting the utility of PDP as a minimally invasive priming strategy that can improve therapeutic outcomes in desmoplastic tumors.

KW - PSMA

KW - extracellular matrix

KW - nanomedicine

KW - photodynamic therapy

KW - prostate cancer

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U2 - 10.1021/acs.nanolett.0c03731

DO - 10.1021/acs.nanolett.0c03731

M3 - Article

C2 - 33301689

AN - SCOPUS:85098774402

SN - 1530-6984

VL - 21

SP - 344

EP - 352

JO - Nano Letters

JF - Nano Letters

IS - 1

ER -

Subtherapeutic Photodynamic Treatment Facilitates Tumor Nanomedicine Delivery and Overcomes Desmoplasia

Abstract

Keywords

ASJC Scopus subject areas

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