Development and Evaluation of a PSMA-Targeted Nanosystem Co-Packaging Docetaxel and Androgen Receptor siRNA for Castration-Resistant Prostate Cancer Treatment
Primary prostate cancer (PC) progresses to castration-resistant PC (CRPC) during androgen deprivation therapy (ADR) in early stages of prostate cancer. Thus, rather than blocking the androgen-related pathway further, docetaxel (DTX)-based therapy has become the most effective and standard first-line...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/14/5/964 |
| _version_ | 1827667319258611712 |
|---|---|
| author | Yingying Zhang Hongxia Duan Heming Zhao Lingling Qi Yanhong Liu Zheao Zhang Chao Liu Liqing Chen Mingji Jin Youyan Guan Zhonggao Gao Wei Huang |
| author_facet | Yingying Zhang Hongxia Duan Heming Zhao Lingling Qi Yanhong Liu Zheao Zhang Chao Liu Liqing Chen Mingji Jin Youyan Guan Zhonggao Gao Wei Huang |
| author_sort | Yingying Zhang |
| collection | DOAJ |
| description | Primary prostate cancer (PC) progresses to castration-resistant PC (CRPC) during androgen deprivation therapy (ADR) in early stages of prostate cancer. Thus, rather than blocking the androgen-related pathway further, docetaxel (DTX)-based therapy has become the most effective and standard first-line chemotherapy for CRPC. Although the therapy is successful in prolonging the survival of patients with CRPC, chemotherapy resistance develops due to the abnormal activation of the androgen receptor (AR) signaling pathway. Thus, to optimize DTX efficacy, continued maximum suppression of androgen levels and AR signaling is required. Here, we designed a prostate-specific membrane antigen (PSMA)-targeted nanosystem to carry both DTX and AR siRNA (Di-PP/AR-siRNA/DTX) for CRPC treatment. Specifically, DTX was encapsulated into the hydrophobic inner layer, and the AR siRNA was then condensed with the cationic PEI block in the hydrophilic outer layer of the PEI-PLGA polymeric micelles. The micelles were further coated with PSMA-targeted anionic polyethylene glycol-polyaspartic acid (Di-PEG-PLD). In vitro and in vivo results demonstrated that the resulting Di-PP/AR-siRNA/DTX exhibited prolonged blood circulation, selective targeting, and enhanced antitumor effects. Consequently, Di-PP/AR-siRNA/DTX holds great potential for efficient CRPC treatment by combining chemotherapy and siRNA silencing of androgen-related signaling pathways. |
| first_indexed | 2024-03-10T03:08:01Z |
| format | Article |
| id | doaj.art-e4e343223b3849978946886821a1dcc3 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:08:01Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-e4e343223b3849978946886821a1dcc32023-11-23T12:37:17ZengMDPI AGPharmaceutics1999-49232022-04-0114596410.3390/pharmaceutics14050964Development and Evaluation of a PSMA-Targeted Nanosystem Co-Packaging Docetaxel and Androgen Receptor siRNA for Castration-Resistant Prostate Cancer TreatmentYingying Zhang0Hongxia Duan1Heming Zhao2Lingling Qi3Yanhong Liu4Zheao Zhang5Chao Liu6Liqing Chen7Mingji Jin8Youyan Guan9Zhonggao Gao10Wei Huang11State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaDepartment of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaPrimary prostate cancer (PC) progresses to castration-resistant PC (CRPC) during androgen deprivation therapy (ADR) in early stages of prostate cancer. Thus, rather than blocking the androgen-related pathway further, docetaxel (DTX)-based therapy has become the most effective and standard first-line chemotherapy for CRPC. Although the therapy is successful in prolonging the survival of patients with CRPC, chemotherapy resistance develops due to the abnormal activation of the androgen receptor (AR) signaling pathway. Thus, to optimize DTX efficacy, continued maximum suppression of androgen levels and AR signaling is required. Here, we designed a prostate-specific membrane antigen (PSMA)-targeted nanosystem to carry both DTX and AR siRNA (Di-PP/AR-siRNA/DTX) for CRPC treatment. Specifically, DTX was encapsulated into the hydrophobic inner layer, and the AR siRNA was then condensed with the cationic PEI block in the hydrophilic outer layer of the PEI-PLGA polymeric micelles. The micelles were further coated with PSMA-targeted anionic polyethylene glycol-polyaspartic acid (Di-PEG-PLD). In vitro and in vivo results demonstrated that the resulting Di-PP/AR-siRNA/DTX exhibited prolonged blood circulation, selective targeting, and enhanced antitumor effects. Consequently, Di-PP/AR-siRNA/DTX holds great potential for efficient CRPC treatment by combining chemotherapy and siRNA silencing of androgen-related signaling pathways.https://www.mdpi.com/1999-4923/14/5/964prostate cancerandrogen receptorsiRNA deliverydocetaxelPSMA targeting |
| spellingShingle | Yingying Zhang Hongxia Duan Heming Zhao Lingling Qi Yanhong Liu Zheao Zhang Chao Liu Liqing Chen Mingji Jin Youyan Guan Zhonggao Gao Wei Huang Development and Evaluation of a PSMA-Targeted Nanosystem Co-Packaging Docetaxel and Androgen Receptor siRNA for Castration-Resistant Prostate Cancer Treatment Pharmaceutics prostate cancer androgen receptor siRNA delivery docetaxel PSMA targeting |
| title | Development and Evaluation of a PSMA-Targeted Nanosystem Co-Packaging Docetaxel and Androgen Receptor siRNA for Castration-Resistant Prostate Cancer Treatment |
| title_full | Development and Evaluation of a PSMA-Targeted Nanosystem Co-Packaging Docetaxel and Androgen Receptor siRNA for Castration-Resistant Prostate Cancer Treatment |
| title_fullStr | Development and Evaluation of a PSMA-Targeted Nanosystem Co-Packaging Docetaxel and Androgen Receptor siRNA for Castration-Resistant Prostate Cancer Treatment |
| title_full_unstemmed | Development and Evaluation of a PSMA-Targeted Nanosystem Co-Packaging Docetaxel and Androgen Receptor siRNA for Castration-Resistant Prostate Cancer Treatment |
| title_short | Development and Evaluation of a PSMA-Targeted Nanosystem Co-Packaging Docetaxel and Androgen Receptor siRNA for Castration-Resistant Prostate Cancer Treatment |
| title_sort | development and evaluation of a psma targeted nanosystem co packaging docetaxel and androgen receptor sirna for castration resistant prostate cancer treatment |
| topic | prostate cancer androgen receptor siRNA delivery docetaxel PSMA targeting |
| url | https://www.mdpi.com/1999-4923/14/5/964 |
| work_keys_str_mv | AT yingyingzhang developmentandevaluationofapsmatargetednanosystemcopackagingdocetaxelandandrogenreceptorsirnaforcastrationresistantprostatecancertreatment AT hongxiaduan developmentandevaluationofapsmatargetednanosystemcopackagingdocetaxelandandrogenreceptorsirnaforcastrationresistantprostatecancertreatment AT hemingzhao developmentandevaluationofapsmatargetednanosystemcopackagingdocetaxelandandrogenreceptorsirnaforcastrationresistantprostatecancertreatment AT linglingqi developmentandevaluationofapsmatargetednanosystemcopackagingdocetaxelandandrogenreceptorsirnaforcastrationresistantprostatecancertreatment AT yanhongliu developmentandevaluationofapsmatargetednanosystemcopackagingdocetaxelandandrogenreceptorsirnaforcastrationresistantprostatecancertreatment AT zheaozhang developmentandevaluationofapsmatargetednanosystemcopackagingdocetaxelandandrogenreceptorsirnaforcastrationresistantprostatecancertreatment AT chaoliu developmentandevaluationofapsmatargetednanosystemcopackagingdocetaxelandandrogenreceptorsirnaforcastrationresistantprostatecancertreatment AT liqingchen developmentandevaluationofapsmatargetednanosystemcopackagingdocetaxelandandrogenreceptorsirnaforcastrationresistantprostatecancertreatment AT mingjijin developmentandevaluationofapsmatargetednanosystemcopackagingdocetaxelandandrogenreceptorsirnaforcastrationresistantprostatecancertreatment AT youyanguan developmentandevaluationofapsmatargetednanosystemcopackagingdocetaxelandandrogenreceptorsirnaforcastrationresistantprostatecancertreatment AT zhonggaogao developmentandevaluationofapsmatargetednanosystemcopackagingdocetaxelandandrogenreceptorsirnaforcastrationresistantprostatecancertreatment AT weihuang developmentandevaluationofapsmatargetednanosystemcopackagingdocetaxelandandrogenreceptorsirnaforcastrationresistantprostatecancertreatment |