Dual pH/reduction-responsive hybrid polymeric micelles for targeted chemo-photothermal combination therapy

[Display omitted] The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed new pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranost...

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Veröffentlicht in:Acta biomaterialia 2018-07, Vol.75, p.371-385
Hauptverfasser: Zhang, Linhua, Qin, Yu, Zhang, Zhiming, Fan, Fan, Huang, Chenlu, Lu, Li, Wang, Hai, Jin, Xu, Zhao, Hanxue, Kong, Deling, Wang, Chun, Sun, Hongfan, Leng, Xigang, Zhu, Dunwan
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container_title Acta biomaterialia
container_volume 75
creator Zhang, Linhua
Qin, Yu
Zhang, Zhiming
Fan, Fan
Huang, Chenlu
Lu, Li
Wang, Hai
Jin, Xu
Zhao, Hanxue
Kong, Deling
Wang, Chun
Sun, Hongfan
Leng, Xigang
Zhu, Dunwan
description [Display omitted] The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed new pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs exhibited nano-sized structure (∼100 nm) with good monodispersity, high encapsulation efficiency of both ICG and DOX, triggered DOX release in response to acid pH and reduction environment, and excellent temperature conversion with laser irradiation. In vitro cellular uptake study indicated FA Co-PMs achieved significant targeting to BEL-7404 cells via folate receptor-mediated endocytosis, and laser-induced hyperthermia further enhanced drug accumulation into cancer cells. In vivo biodistribution study indicated that FA Co-PMs prolonged drug circulation and enhanced drug accumulation into the tumor via EPR effect and FA targeting. Furthermore, the ICG-based photo-triggered hyperthermia combined with DOX-based chemotherapy synergistically induced the BEL-7404 cell death and apoptosis, and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs were promising theranostic nanocarriers for versatile antitumor drug delivery and imaging-guided cancer chemo-photothermal combination therapy. The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed novel pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs triggered DOX release in response to acid pH and reduction environment and exhibited excellent temperature conversion with laser irradiation. The results indicated FA Co-PMs achieved significant targeting to BEL-7404 cells in vitro and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs displayed great potential in imaging-guided cancer chemo-photothermal combination therapy as
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Herein, we designed new pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs exhibited nano-sized structure (∼100 nm) with good monodispersity, high encapsulation efficiency of both ICG and DOX, triggered DOX release in response to acid pH and reduction environment, and excellent temperature conversion with laser irradiation. In vitro cellular uptake study indicated FA Co-PMs achieved significant targeting to BEL-7404 cells via folate receptor-mediated endocytosis, and laser-induced hyperthermia further enhanced drug accumulation into cancer cells. In vivo biodistribution study indicated that FA Co-PMs prolonged drug circulation and enhanced drug accumulation into the tumor via EPR effect and FA targeting. Furthermore, the ICG-based photo-triggered hyperthermia combined with DOX-based chemotherapy synergistically induced the BEL-7404 cell death and apoptosis, and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs were promising theranostic nanocarriers for versatile antitumor drug delivery and imaging-guided cancer chemo-photothermal combination therapy. The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed novel pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs triggered DOX release in response to acid pH and reduction environment and exhibited excellent temperature conversion with laser irradiation. The results indicated FA Co-PMs achieved significant targeting to BEL-7404 cells in vitro and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs displayed great potential in imaging-guided cancer chemo-photothermal combination therapy as theranostic nanocarriers.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2018.05.026</identifier><identifier>PMID: 29777957</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Accumulation ; Animals ; Apoptosis ; Biocompatibility ; Cancer ; Cell death ; Cell Line, Tumor ; Cells ; Chemo-photothermal therapy ; Chemotherapy ; Delayed-Action Preparations - chemistry ; Delayed-Action Preparations - pharmacokinetics ; Delayed-Action Preparations - pharmacology ; Doxorubicin ; Doxorubicin - chemistry ; Doxorubicin - pharmacokinetics ; Doxorubicin - pharmacology ; Drug delivery ; Drug delivery systems ; Dual-responsive ; Encapsulation ; Endocytosis ; Female ; Folic acid ; Humans ; Hybrid polymeric micelles ; Hyperthermia ; Hyperthermia, Induced ; In vivo methods and tests ; Indocyanine green ; Indocyanine Green - chemistry ; Indocyanine Green - pharmacokinetics ; Indocyanine Green - pharmacology ; Irradiation ; Liver Neoplasms, Experimental - diagnostic imaging ; Liver Neoplasms, Experimental - metabolism ; Liver Neoplasms, Experimental - therapy ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Micelles ; Molecules ; Optical Imaging ; pH effects ; Phototherapy ; Photothermal conversion ; Polymers ; Reduction ; Toxicity ; Tumors ; Xenograft Model Antitumor Assays ; Xenografts</subject><ispartof>Acta biomaterialia, 2018-07, Vol.75, p.371-385</ispartof><rights>2018 Acta Materialia Inc.</rights><rights>Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier BV Jul 15, 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-bafc3e0028db9c8c54fe833e2601ccf6bfd601b3d62fca33efab7a8b9896276a3</citedby><cites>FETCH-LOGICAL-c390t-bafc3e0028db9c8c54fe833e2601ccf6bfd601b3d62fca33efab7a8b9896276a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1742706118302952$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29777957$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Linhua</creatorcontrib><creatorcontrib>Qin, Yu</creatorcontrib><creatorcontrib>Zhang, Zhiming</creatorcontrib><creatorcontrib>Fan, Fan</creatorcontrib><creatorcontrib>Huang, Chenlu</creatorcontrib><creatorcontrib>Lu, Li</creatorcontrib><creatorcontrib>Wang, Hai</creatorcontrib><creatorcontrib>Jin, Xu</creatorcontrib><creatorcontrib>Zhao, Hanxue</creatorcontrib><creatorcontrib>Kong, Deling</creatorcontrib><creatorcontrib>Wang, Chun</creatorcontrib><creatorcontrib>Sun, Hongfan</creatorcontrib><creatorcontrib>Leng, Xigang</creatorcontrib><creatorcontrib>Zhu, Dunwan</creatorcontrib><title>Dual pH/reduction-responsive hybrid polymeric micelles for targeted chemo-photothermal combination therapy</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>[Display omitted] The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed new pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs exhibited nano-sized structure (∼100 nm) with good monodispersity, high encapsulation efficiency of both ICG and DOX, triggered DOX release in response to acid pH and reduction environment, and excellent temperature conversion with laser irradiation. In vitro cellular uptake study indicated FA Co-PMs achieved significant targeting to BEL-7404 cells via folate receptor-mediated endocytosis, and laser-induced hyperthermia further enhanced drug accumulation into cancer cells. In vivo biodistribution study indicated that FA Co-PMs prolonged drug circulation and enhanced drug accumulation into the tumor via EPR effect and FA targeting. Furthermore, the ICG-based photo-triggered hyperthermia combined with DOX-based chemotherapy synergistically induced the BEL-7404 cell death and apoptosis, and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs were promising theranostic nanocarriers for versatile antitumor drug delivery and imaging-guided cancer chemo-photothermal combination therapy. The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed novel pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs triggered DOX release in response to acid pH and reduction environment and exhibited excellent temperature conversion with laser irradiation. The results indicated FA Co-PMs achieved significant targeting to BEL-7404 cells in vitro and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs displayed great potential in imaging-guided cancer chemo-photothermal combination therapy as theranostic nanocarriers.</description><subject>Accumulation</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biocompatibility</subject><subject>Cancer</subject><subject>Cell death</subject><subject>Cell Line, Tumor</subject><subject>Cells</subject><subject>Chemo-photothermal therapy</subject><subject>Chemotherapy</subject><subject>Delayed-Action Preparations - chemistry</subject><subject>Delayed-Action Preparations - pharmacokinetics</subject><subject>Delayed-Action Preparations - pharmacology</subject><subject>Doxorubicin</subject><subject>Doxorubicin - chemistry</subject><subject>Doxorubicin - pharmacokinetics</subject><subject>Doxorubicin - pharmacology</subject><subject>Drug delivery</subject><subject>Drug delivery systems</subject><subject>Dual-responsive</subject><subject>Encapsulation</subject><subject>Endocytosis</subject><subject>Female</subject><subject>Folic acid</subject><subject>Humans</subject><subject>Hybrid polymeric micelles</subject><subject>Hyperthermia</subject><subject>Hyperthermia, Induced</subject><subject>In vivo methods and tests</subject><subject>Indocyanine green</subject><subject>Indocyanine Green - chemistry</subject><subject>Indocyanine Green - pharmacokinetics</subject><subject>Indocyanine Green - pharmacology</subject><subject>Irradiation</subject><subject>Liver Neoplasms, Experimental - diagnostic imaging</subject><subject>Liver Neoplasms, Experimental - metabolism</subject><subject>Liver Neoplasms, Experimental - therapy</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Micelles</subject><subject>Molecules</subject><subject>Optical Imaging</subject><subject>pH effects</subject><subject>Phototherapy</subject><subject>Photothermal conversion</subject><subject>Polymers</subject><subject>Reduction</subject><subject>Toxicity</subject><subject>Tumors</subject><subject>Xenograft Model Antitumor Assays</subject><subject>Xenografts</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctu1TAQhqMK1Bu8AUKR2LBJ6ktiOxskVFqKVIkNrC1fxhxHSRxsp9J5exydlgULVjOa-eaf0fxV9Q6jFiPMbsZWmax9aAnCokV9iwg7qy6x4KLhPROvSs470nDE8EV1ldKIEBWYiPPqggyc86Hnl9X4ZVNTvT7cRLCbyT4sTYS0hiX5J6gPRx29rdcwHWeI3tSzNzBNkGoXYp1V_AUZbG0OMIdmPYQc8gHiXBRNmLVf1C5Y7zW1Ht9Ur52aErx9jtfVz_u7H7cPzeP3r99uPz82hg4oN1o5QwEhIqwejDB950BQCoQhbIxj2tmSaWoZcUaVhlOaK6EHMTDCmaLX1ceT7hrD7w1SlrNP-9lqgbAlSVBHCEU97Qr64R90DFtcynWFGjjrGUG0UN2JMjGkFMHJNfpZxaPESO5eyFGevJC7FxL1snhRxt4_i296Bvt36OX5Bfh0AqB848lDlMl4WAxYH8FkaYP__4Y_UNmfGw</recordid><startdate>20180715</startdate><enddate>20180715</enddate><creator>Zhang, Linhua</creator><creator>Qin, Yu</creator><creator>Zhang, Zhiming</creator><creator>Fan, Fan</creator><creator>Huang, Chenlu</creator><creator>Lu, Li</creator><creator>Wang, Hai</creator><creator>Jin, Xu</creator><creator>Zhao, Hanxue</creator><creator>Kong, Deling</creator><creator>Wang, Chun</creator><creator>Sun, Hongfan</creator><creator>Leng, Xigang</creator><creator>Zhu, Dunwan</creator><general>Elsevier Ltd</general><general>Elsevier BV</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20180715</creationdate><title>Dual pH/reduction-responsive hybrid polymeric micelles for targeted chemo-photothermal combination therapy</title><author>Zhang, Linhua ; Qin, Yu ; Zhang, Zhiming ; Fan, Fan ; Huang, Chenlu ; Lu, Li ; Wang, Hai ; Jin, Xu ; Zhao, Hanxue ; Kong, Deling ; Wang, Chun ; Sun, Hongfan ; Leng, Xigang ; Zhu, Dunwan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-bafc3e0028db9c8c54fe833e2601ccf6bfd601b3d62fca33efab7a8b9896276a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Accumulation</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biocompatibility</topic><topic>Cancer</topic><topic>Cell death</topic><topic>Cell Line, Tumor</topic><topic>Cells</topic><topic>Chemo-photothermal therapy</topic><topic>Chemotherapy</topic><topic>Delayed-Action Preparations - chemistry</topic><topic>Delayed-Action Preparations - pharmacokinetics</topic><topic>Delayed-Action Preparations - pharmacology</topic><topic>Doxorubicin</topic><topic>Doxorubicin - chemistry</topic><topic>Doxorubicin - pharmacokinetics</topic><topic>Doxorubicin - pharmacology</topic><topic>Drug delivery</topic><topic>Drug delivery systems</topic><topic>Dual-responsive</topic><topic>Encapsulation</topic><topic>Endocytosis</topic><topic>Female</topic><topic>Folic acid</topic><topic>Humans</topic><topic>Hybrid polymeric micelles</topic><topic>Hyperthermia</topic><topic>Hyperthermia, Induced</topic><topic>In vivo methods and tests</topic><topic>Indocyanine green</topic><topic>Indocyanine Green - chemistry</topic><topic>Indocyanine Green - pharmacokinetics</topic><topic>Indocyanine Green - pharmacology</topic><topic>Irradiation</topic><topic>Liver Neoplasms, Experimental - diagnostic imaging</topic><topic>Liver Neoplasms, Experimental - metabolism</topic><topic>Liver Neoplasms, Experimental - therapy</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Micelles</topic><topic>Molecules</topic><topic>Optical Imaging</topic><topic>pH effects</topic><topic>Phototherapy</topic><topic>Photothermal conversion</topic><topic>Polymers</topic><topic>Reduction</topic><topic>Toxicity</topic><topic>Tumors</topic><topic>Xenograft Model Antitumor Assays</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Linhua</creatorcontrib><creatorcontrib>Qin, Yu</creatorcontrib><creatorcontrib>Zhang, Zhiming</creatorcontrib><creatorcontrib>Fan, Fan</creatorcontrib><creatorcontrib>Huang, Chenlu</creatorcontrib><creatorcontrib>Lu, Li</creatorcontrib><creatorcontrib>Wang, Hai</creatorcontrib><creatorcontrib>Jin, Xu</creatorcontrib><creatorcontrib>Zhao, Hanxue</creatorcontrib><creatorcontrib>Kong, Deling</creatorcontrib><creatorcontrib>Wang, Chun</creatorcontrib><creatorcontrib>Sun, Hongfan</creatorcontrib><creatorcontrib>Leng, Xigang</creatorcontrib><creatorcontrib>Zhu, Dunwan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics &amp; 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Herein, we designed new pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs exhibited nano-sized structure (∼100 nm) with good monodispersity, high encapsulation efficiency of both ICG and DOX, triggered DOX release in response to acid pH and reduction environment, and excellent temperature conversion with laser irradiation. In vitro cellular uptake study indicated FA Co-PMs achieved significant targeting to BEL-7404 cells via folate receptor-mediated endocytosis, and laser-induced hyperthermia further enhanced drug accumulation into cancer cells. In vivo biodistribution study indicated that FA Co-PMs prolonged drug circulation and enhanced drug accumulation into the tumor via EPR effect and FA targeting. Furthermore, the ICG-based photo-triggered hyperthermia combined with DOX-based chemotherapy synergistically induced the BEL-7404 cell death and apoptosis, and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs were promising theranostic nanocarriers for versatile antitumor drug delivery and imaging-guided cancer chemo-photothermal combination therapy. The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed novel pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs triggered DOX release in response to acid pH and reduction environment and exhibited excellent temperature conversion with laser irradiation. The results indicated FA Co-PMs achieved significant targeting to BEL-7404 cells in vitro and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs displayed great potential in imaging-guided cancer chemo-photothermal combination therapy as theranostic nanocarriers.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>29777957</pmid><doi>10.1016/j.actbio.2018.05.026</doi><tpages>15</tpages></addata></record>
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subjects Accumulation
Animals
Apoptosis
Biocompatibility
Cancer
Cell death
Cell Line, Tumor
Cells
Chemo-photothermal therapy
Chemotherapy
Delayed-Action Preparations - chemistry
Delayed-Action Preparations - pharmacokinetics
Delayed-Action Preparations - pharmacology
Doxorubicin
Doxorubicin - chemistry
Doxorubicin - pharmacokinetics
Doxorubicin - pharmacology
Drug delivery
Drug delivery systems
Dual-responsive
Encapsulation
Endocytosis
Female
Folic acid
Humans
Hybrid polymeric micelles
Hyperthermia
Hyperthermia, Induced
In vivo methods and tests
Indocyanine green
Indocyanine Green - chemistry
Indocyanine Green - pharmacokinetics
Indocyanine Green - pharmacology
Irradiation
Liver Neoplasms, Experimental - diagnostic imaging
Liver Neoplasms, Experimental - metabolism
Liver Neoplasms, Experimental - therapy
Mice
Mice, Inbred BALB C
Mice, Nude
Micelles
Molecules
Optical Imaging
pH effects
Phototherapy
Photothermal conversion
Polymers
Reduction
Toxicity
Tumors
Xenograft Model Antitumor Assays
Xenografts
title Dual pH/reduction-responsive hybrid polymeric micelles for targeted chemo-photothermal combination therapy
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