GRP78-targeted and doxorubicin-loaded nanodroplets combined with ultrasound: a potential novel theranostics for castration-resistant prostate cancer

The construction of multifunctional oncotherapy nanoplatforms that combine diagnosis and treatment remains challenging. Nanodroplets (NDs), which simultaneously enhance ultrasound imaging and therapeutic effects, are a potential strategy for non-invasive drug delivery. To achieve the goals of precis...

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Main Authors: Yading Zhao, Dandan Shi, Mengmeng Shang, Xiao Sun, Lu Guo, Dong Meng, Xinxin Liu, Xiaoying Zhou, Jie Li
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Drug Delivery
Subjects:
Online Access:http://dx.doi.org/10.1080/10717544.2021.2023698
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author Yading Zhao
Dandan Shi
Mengmeng Shang
Xiao Sun
Lu Guo
Dong Meng
Xinxin Liu
Xiaoying Zhou
Jie Li
author_facet Yading Zhao
Dandan Shi
Mengmeng Shang
Xiao Sun
Lu Guo
Dong Meng
Xinxin Liu
Xiaoying Zhou
Jie Li
author_sort Yading Zhao
collection DOAJ
description The construction of multifunctional oncotherapy nanoplatforms that combine diagnosis and treatment remains challenging. Nanodroplets (NDs), which simultaneously enhance ultrasound imaging and therapeutic effects, are a potential strategy for non-invasive drug delivery. To achieve the goals of precise medicine, novel SP94 peptide-modified and doxorubicin-loaded ultrasonic NDs (SP94-DOX-NDs) for castration-resistant prostate cancer (CRPC) targeting and treatment were constructed in this study. The characteristics, contrast-enhanced ultrasound imaging (CEUI), targeting ability to glucose-regulated protein 78 (GRP78)-overexpressing CRPC and anticancer effect of the SP94-DOX-NDs were assessed. The desired SP94-NDs were successfully prepared using the nanoemulsification method using a certain proportion of SP94-PEG-chitosan, perfluoropentane (PFP), Tween 20, and lecithin. SP94-NDs with a size of ∼300 nm showed great biocompatibility and CEUI ability. Compared with blank NDs, SP94-NDs exhibited higher tumor-specific targeting ability due to conjugation between the SP94 peptide and GRP78-overexpressing 22RV1 cells. Most importantly, in vitro and in vivo investigations showed that SP94-DOX-NDs combined with ultrasound could specifically deliver DOX into 22RV1 cells and thereby demonstrated a stronger anticancer effect than DOX-NDs and DOX. Thus, SP94-DOX-NDs may provide an efficient approach for the real-time imaging of tumors and triggered, accurate drug delivery to tumors.
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spelling doaj.art-a140a6ea7d48464181361bec2869677e2022-12-21T21:19:28ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642022-12-0129120321310.1080/10717544.2021.20236982023698GRP78-targeted and doxorubicin-loaded nanodroplets combined with ultrasound: a potential novel theranostics for castration-resistant prostate cancerYading Zhao0Dandan Shi1Mengmeng Shang2Xiao Sun3Lu Guo4Dong Meng5Xinxin Liu6Xiaoying Zhou7Jie Li8Department of Ultrasound, Qilu Hospital of Shandong UniversityDepartment of Ultrasound, Qilu Hospital of Shandong UniversityDepartment of Ultrasound, Qilu Hospital of Shandong UniversityDepartment of Ultrasound, Qilu Hospital of Shandong UniversityDepartment of Ultrasound, Qilu Hospital of Shandong UniversityDepartment of Ultrasound, Qilu Hospital of Shandong UniversityDepartment of Ultrasound, Qilu Hospital of Shandong UniversityDepartment of Ultrasound, Qilu Hospital of Shandong UniversityDepartment of Ultrasound, Qilu Hospital of Shandong UniversityThe construction of multifunctional oncotherapy nanoplatforms that combine diagnosis and treatment remains challenging. Nanodroplets (NDs), which simultaneously enhance ultrasound imaging and therapeutic effects, are a potential strategy for non-invasive drug delivery. To achieve the goals of precise medicine, novel SP94 peptide-modified and doxorubicin-loaded ultrasonic NDs (SP94-DOX-NDs) for castration-resistant prostate cancer (CRPC) targeting and treatment were constructed in this study. The characteristics, contrast-enhanced ultrasound imaging (CEUI), targeting ability to glucose-regulated protein 78 (GRP78)-overexpressing CRPC and anticancer effect of the SP94-DOX-NDs were assessed. The desired SP94-NDs were successfully prepared using the nanoemulsification method using a certain proportion of SP94-PEG-chitosan, perfluoropentane (PFP), Tween 20, and lecithin. SP94-NDs with a size of ∼300 nm showed great biocompatibility and CEUI ability. Compared with blank NDs, SP94-NDs exhibited higher tumor-specific targeting ability due to conjugation between the SP94 peptide and GRP78-overexpressing 22RV1 cells. Most importantly, in vitro and in vivo investigations showed that SP94-DOX-NDs combined with ultrasound could specifically deliver DOX into 22RV1 cells and thereby demonstrated a stronger anticancer effect than DOX-NDs and DOX. Thus, SP94-DOX-NDs may provide an efficient approach for the real-time imaging of tumors and triggered, accurate drug delivery to tumors.http://dx.doi.org/10.1080/10717544.2021.2023698nanodropletsglucose-regulated protein 78ultrasound imagingtheranosticscastration-resistant prostate cancer
spellingShingle Yading Zhao
Dandan Shi
Mengmeng Shang
Xiao Sun
Lu Guo
Dong Meng
Xinxin Liu
Xiaoying Zhou
Jie Li
GRP78-targeted and doxorubicin-loaded nanodroplets combined with ultrasound: a potential novel theranostics for castration-resistant prostate cancer
Drug Delivery
nanodroplets
glucose-regulated protein 78
ultrasound imaging
theranostics
castration-resistant prostate cancer
title GRP78-targeted and doxorubicin-loaded nanodroplets combined with ultrasound: a potential novel theranostics for castration-resistant prostate cancer
title_full GRP78-targeted and doxorubicin-loaded nanodroplets combined with ultrasound: a potential novel theranostics for castration-resistant prostate cancer
title_fullStr GRP78-targeted and doxorubicin-loaded nanodroplets combined with ultrasound: a potential novel theranostics for castration-resistant prostate cancer
title_full_unstemmed GRP78-targeted and doxorubicin-loaded nanodroplets combined with ultrasound: a potential novel theranostics for castration-resistant prostate cancer
title_short GRP78-targeted and doxorubicin-loaded nanodroplets combined with ultrasound: a potential novel theranostics for castration-resistant prostate cancer
title_sort grp78 targeted and doxorubicin loaded nanodroplets combined with ultrasound a potential novel theranostics for castration resistant prostate cancer
topic nanodroplets
glucose-regulated protein 78
ultrasound imaging
theranostics
castration-resistant prostate cancer
url http://dx.doi.org/10.1080/10717544.2021.2023698
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