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Delivery of gefitinib loaded nanoparticles for effectively inhibiting prostate cancer progression
Zhi Xiong1,2, Tong Tong3, Zhaoxiang Xie1,2
1Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. likw6@mail.sysu.edu.cn.
Abstract:
Androgen deprivation therapy is administered to suppress the growth of prostate cancer (PCa). However, some cells continue to proliferate independent of hormones, leading to the development of castration-resistant prostate cancer (CRPC). Overexpression of the epidermal growth factor receptor (EGFR) has been observed in CRPC and is associated with an unfavorable prognosis. Gefitinib (GEF) is an EGFR inhibitor used to treat patients with CRPC. Nevertheless, some clinical studies have reported that gefitinib does not result in prostate-specific antigen (PSA) or objectively measurable CRPC reactions. This lack of response may be attributed to the limited solubility in water, high side effects, low tumor aggregation, and insufficient tumor-specific reactions of GEF. In order to tackle these obstacles, we present a practical and efficient approach to administer GEF, encompassing the utilization of biocompatible nanostructures as a vehicle for drug delivery to augment its bioaccessibility and curative potency. Despite their small particle size, poly(D,L-lactide-co-glycolide) acid nanoparticles (PLGA NPs) exhibit a high drug-loading capacity, low toxicity, biocompatibility, biodegradability, and minimal immunogenicity. The drug delivery efficiency can be improved by employing GEF@PLGA NPs, which could also enhance drug cytotoxicity and impede the advancement of prostate cancer. Moreover, through experiments in vivo, it has been verified that GEF@PLGA NPs exhibit selective accumulation in the tumor and effectively restrain tumor growth. Therefore, the GEF@PLGA NPs hold great promise for the treatment of PCa.
Insights
This study developed novel nanoparticles for Gefitinib (GEF) delivery to treat castration-resistant prostate cancer (CRPC). GEF-loaded nanoparticles effectively targeted tumors and inhibited cancer growth, offering a promising new therapeutic strategy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Androgen deprivation therapy is standard for prostate cancer (PCa), but castration-resistant PCa (CRPC) develops.
- Epidermal growth factor receptor (EGFR) overexpression in CRPC correlates with poor prognosis.
- Gefitinib (GEF), an EGFR inhibitor, shows limited efficacy in CRPC due to poor solubility and tumor targeting.
Purpose of the Study:
- To develop an efficient drug delivery system for Gefitinib (GEF) to overcome its limitations in treating castration-resistant prostate cancer (CRPC).
- To enhance the bioaccessibility, curative potency, and tumor-specific delivery of GEF using biocompatible nanostructures.
Main Methods:
- Gefitinib (GEF) was encapsulated into poly(D,L-lactide-co-glycolide) acid nanoparticles (PLGA NPs) to create GEF@PLGA NPs.
- Characterization of GEF@PLGA NPs for drug-loading capacity, toxicity, biocompatibility, and biodegradability.
- In vivo studies were conducted to evaluate tumor targeting, growth inhibition, and therapeutic efficacy of GEF@PLGA NPs in CRPC models.
Main Results:
- GEF@PLGA NPs demonstrated high drug-loading capacity, low toxicity, and excellent biocompatibility.
- In vivo experiments confirmed selective accumulation of GEF@PLGA NPs in tumors.
- GEF@PLGA NPs effectively restrained tumor growth and enhanced GEF's anti-cancer activity in CRPC models.
Conclusions:
- GEF@PLGA NPs represent a promising nanocarrier system for improving Gefitinib delivery in prostate cancer treatment.
- This approach enhances drug bioavailability and therapeutic efficacy while minimizing side effects.
- GEF@PLGA NPs hold significant potential for the effective management of castration-resistant prostate cancer.
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