Acid-Triggered Nanoexpansion Polymeric Micelles for Enhanced Photodynamic Therapy
Photodynamic therapy (PDT) as a noninvasive and selective treatment technology has presented great potential in cancer prevention and precision medicine, but its therapeutic efficacy is still greatly inhibited by the limitations of photosensitizers (PSs) in the microenvironment such as the aggregati...
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| Published in | ACS applied materials & interfaces Vol. 11; no. 37; pp. 33697 - 33705 |
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| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
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United States
American Chemical Society
18.09.2019
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| Abstract | Photodynamic therapy (PDT) as a noninvasive and selective treatment technology has presented great potential in cancer prevention and precision medicine, but its therapeutic efficacy is still greatly inhibited by the limitations of photosensitizers (PSs) in the microenvironment such as the aggregation caused quenching (ACQ) of PSs. Herein, we proposed an “acid-triggered nanoexpansion” method to further reduce the aggregation of photosensitizers by constructing acetal-based polymeric micelles. A pH-responsive amphiphilic block copolymer, POEGMA-b-[PTTMA-co-PTPPC6MA] was synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization and self-assembled into spherical micelles. In the normal physiological environment, the micelles were stable and had good biocompatibility. Upon entry into the acidic microenvironment of the tumor, the acid-responsive hydrophobic 2, 4, 6-trimethoxybenzaldehyde in the micelles hydrolyzed and generated a hydrophilic diol moiety. Although the hydrophility of the micellar core was increased, the assembled structure of block copolymers was not dissociated but expanded. The responsive expansion of the micelles could allow the photosensitizers to well-disperse in the core, whereas more tumor-dissolved oxygen entered the micelles. This phenomenon could provide a better nanoenvironment for photosensitizers to reduce the ACQ of the photosensitizers, leading to more singlet oxygen (1O2) produced under the laser irradiation (650 nm). Both in vitro and in vivo studies have demonstrated that the remarkable photodynamic therapeutic efficacy of acid-responsive micelles could be realized. Thus, the acid-triggered nanoexpansion method might provide more possibilities to develop efficient platforms for treating cancers. |
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| AbstractList | Photodynamic therapy (PDT) as a noninvasive and selective treatment technology has presented great potential in cancer prevention and precision medicine, but its therapeutic efficacy is still greatly inhibited by the limitations of photosensitizers (PSs) in the microenvironment such as the aggregation caused quenching (ACQ) of PSs. Herein, we proposed an “acid-triggered nanoexpansion” method to further reduce the aggregation of photosensitizers by constructing acetal-based polymeric micelles. A pH-responsive amphiphilic block copolymer, POEGMA-b-[PTTMA-co-PTPPC6MA] was synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization and self-assembled into spherical micelles. In the normal physiological environment, the micelles were stable and had good biocompatibility. Upon entry into the acidic microenvironment of the tumor, the acid-responsive hydrophobic 2, 4, 6-trimethoxybenzaldehyde in the micelles hydrolyzed and generated a hydrophilic diol moiety. Although the hydrophility of the micellar core was increased, the assembled structure of block copolymers was not dissociated but expanded. The responsive expansion of the micelles could allow the photosensitizers to well-disperse in the core, whereas more tumor-dissolved oxygen entered the micelles. This phenomenon could provide a better nanoenvironment for photosensitizers to reduce the ACQ of the photosensitizers, leading to more singlet oxygen (¹O₂) produced under the laser irradiation (650 nm). Both in vitro and in vivo studies have demonstrated that the remarkable photodynamic therapeutic efficacy of acid-responsive micelles could be realized. Thus, the acid-triggered nanoexpansion method might provide more possibilities to develop efficient platforms for treating cancers. Photodynamic therapy (PDT) as a noninvasive and selective treatment technology has presented great potential in cancer prevention and precision medicine, but its therapeutic efficacy is still greatly inhibited by the limitations of photosensitizers (PSs) in the microenvironment such as the aggregation caused quenching (ACQ) of PSs. Herein, we proposed an “acid-triggered nanoexpansion” method to further reduce the aggregation of photosensitizers by constructing acetal-based polymeric micelles. A pH-responsive amphiphilic block copolymer, POEGMA-b-[PTTMA-co-PTPPC6MA] was synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization and self-assembled into spherical micelles. In the normal physiological environment, the micelles were stable and had good biocompatibility. Upon entry into the acidic microenvironment of the tumor, the acid-responsive hydrophobic 2, 4, 6-trimethoxybenzaldehyde in the micelles hydrolyzed and generated a hydrophilic diol moiety. Although the hydrophility of the micellar core was increased, the assembled structure of block copolymers was not dissociated but expanded. The responsive expansion of the micelles could allow the photosensitizers to well-disperse in the core, whereas more tumor-dissolved oxygen entered the micelles. This phenomenon could provide a better nanoenvironment for photosensitizers to reduce the ACQ of the photosensitizers, leading to more singlet oxygen (1O2) produced under the laser irradiation (650 nm). Both in vitro and in vivo studies have demonstrated that the remarkable photodynamic therapeutic efficacy of acid-responsive micelles could be realized. Thus, the acid-triggered nanoexpansion method might provide more possibilities to develop efficient platforms for treating cancers. Photodynamic therapy (PDT) as a noninvasive and selective treatment technology has presented great potential in cancer prevention and precision medicine, but its therapeutic efficacy is still greatly inhibited by the limitations of photosensitizers (PSs) in the microenvironment such as the aggregation caused quenching (ACQ) of PSs. Herein, we proposed an "acid-triggered nanoexpansion" method to further reduce the aggregation of photosensitizers by constructing acetal-based polymeric micelles. A pH-responsive amphiphilic block copolymer, POEGMA- -[PTTMA- -PTPPC6MA] was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization and self-assembled into spherical micelles. In the normal physiological environment, the micelles were stable and had good biocompatibility. Upon entry into the acidic microenvironment of the tumor, the acid-responsive hydrophobic 2, 4, 6-trimethoxybenzaldehyde in the micelles hydrolyzed and generated a hydrophilic diol moiety. Although the hydrophility of the micellar core was increased, the assembled structure of block copolymers was not dissociated but expanded. The responsive expansion of the micelles could allow the photosensitizers to well-disperse in the core, whereas more tumor-dissolved oxygen entered the micelles. This phenomenon could provide a better nanoenvironment for photosensitizers to reduce the ACQ of the photosensitizers, leading to more singlet oxygen ( O ) produced under the laser irradiation (650 nm). Both in vitro and in vivo studies have demonstrated that the remarkable photodynamic therapeutic efficacy of acid-responsive micelles could be realized. Thus, the acid-triggered nanoexpansion method might provide more possibilities to develop efficient platforms for treating cancers. Photodynamic therapy (PDT) as a noninvasive and selective treatment technology has presented great potential in cancer prevention and precision medicine, but its therapeutic efficacy is still greatly inhibited by the limitations of photosensitizers (PSs) in the microenvironment such as the aggregation caused quenching (ACQ) of PSs. Herein, we proposed an "acid-triggered nanoexpansion" method to further reduce the aggregation of photosensitizers by constructing acetal-based polymeric micelles. A pH-responsive amphiphilic block copolymer, POEGMA-b-[PTTMA-co-PTPPC6MA] was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization and self-assembled into spherical micelles. In the normal physiological environment, the micelles were stable and had good biocompatibility. Upon entry into the acidic microenvironment of the tumor, the acid-responsive hydrophobic 2, 4, 6-trimethoxybenzaldehyde in the micelles hydrolyzed and generated a hydrophilic diol moiety. Although the hydrophility of the micellar core was increased, the assembled structure of block copolymers was not dissociated but expanded. The responsive expansion of the micelles could allow the photosensitizers to well-disperse in the core, whereas more tumor-dissolved oxygen entered the micelles. This phenomenon could provide a better nanoenvironment for photosensitizers to reduce the ACQ of the photosensitizers, leading to more singlet oxygen (1O2) produced under the laser irradiation (650 nm). Both in vitro and in vivo studies have demonstrated that the remarkable photodynamic therapeutic efficacy of acid-responsive micelles could be realized. Thus, the acid-triggered nanoexpansion method might provide more possibilities to develop efficient platforms for treating cancers.Photodynamic therapy (PDT) as a noninvasive and selective treatment technology has presented great potential in cancer prevention and precision medicine, but its therapeutic efficacy is still greatly inhibited by the limitations of photosensitizers (PSs) in the microenvironment such as the aggregation caused quenching (ACQ) of PSs. Herein, we proposed an "acid-triggered nanoexpansion" method to further reduce the aggregation of photosensitizers by constructing acetal-based polymeric micelles. A pH-responsive amphiphilic block copolymer, POEGMA-b-[PTTMA-co-PTPPC6MA] was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization and self-assembled into spherical micelles. In the normal physiological environment, the micelles were stable and had good biocompatibility. Upon entry into the acidic microenvironment of the tumor, the acid-responsive hydrophobic 2, 4, 6-trimethoxybenzaldehyde in the micelles hydrolyzed and generated a hydrophilic diol moiety. Although the hydrophility of the micellar core was increased, the assembled structure of block copolymers was not dissociated but expanded. The responsive expansion of the micelles could allow the photosensitizers to well-disperse in the core, whereas more tumor-dissolved oxygen entered the micelles. This phenomenon could provide a better nanoenvironment for photosensitizers to reduce the ACQ of the photosensitizers, leading to more singlet oxygen (1O2) produced under the laser irradiation (650 nm). Both in vitro and in vivo studies have demonstrated that the remarkable photodynamic therapeutic efficacy of acid-responsive micelles could be realized. Thus, the acid-triggered nanoexpansion method might provide more possibilities to develop efficient platforms for treating cancers. |
| Author | Zhang, Weian Yang, Guoliang Cao, Hongliang Xu, Beijian Chen, Chao Zhu, Yucheng Gao, Yun Zhong, Sheng Luo, Yaoqin |
| AuthorAffiliation | State Key Laboratory of Bioreactor Engineering, Biomedical Nanotechnology Center, School of Biotechnology Shanghai Key Laboratory of Functional Materials Chemistry, School of Materials Science and Engineering |
| AuthorAffiliation_xml | – name: State Key Laboratory of Bioreactor Engineering, Biomedical Nanotechnology Center, School of Biotechnology – name: Shanghai Key Laboratory of Functional Materials Chemistry, School of Materials Science and Engineering |
| Author_xml | – sequence: 1 givenname: Sheng surname: Zhong fullname: Zhong, Sheng – sequence: 2 givenname: Chao surname: Chen fullname: Chen, Chao – sequence: 3 givenname: Guoliang surname: Yang fullname: Yang, Guoliang – sequence: 4 givenname: Yucheng surname: Zhu fullname: Zhu, Yucheng – sequence: 5 givenname: Hongliang orcidid: 0000-0002-9342-7980 surname: Cao fullname: Cao, Hongliang email: caohl@ecust.edu.cn – sequence: 6 givenname: Beijian surname: Xu fullname: Xu, Beijian – sequence: 7 givenname: Yaoqin surname: Luo fullname: Luo, Yaoqin – sequence: 8 givenname: Yun surname: Gao fullname: Gao, Yun – sequence: 9 givenname: Weian orcidid: 0000-0002-1717-597X surname: Zhang fullname: Zhang, Weian email: wazhang@ecust.edu.cn |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31487149$$D View this record in MEDLINE/PubMed |
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| Keywords | acid-triggered nanoexpansion porphyrin aggregation caused quenching (ACQ) RAFT polymerization photodynamic therapy |
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| Title | Acid-Triggered Nanoexpansion Polymeric Micelles for Enhanced Photodynamic Therapy |
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