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Prostate cancer (PCa) with a high incidence worldwide is a serious threat to men's health. Despite the continuous development of treatment strategies for PCa in recent years, the long-term prognosis of patients is still poor. Hence, the discovery and development of novel, secure, and efficient therapeutic approaches hold significant clinical significance. Although sorafenib (SOR) displays potential as a therapeutic option for PCa, its clinical efficacy is hindered by drug resistance, limited water solubility, and rapid metabolism. Therefore, we proposed to prepare nanoparticles (named SOR@8P4 NPs) utilizing the phenylalanine-based poly(ester amide) polymer (8P4) as the drug carrier to enhance the solubility and drug stability of SOR and improve the therapeutic targeting and bioavailability. SOR@8P4 NPs had high stability and showed acid-responsive drug release at the acidic tumor microenvironment. Additionally, SOR@8P4 NPs demonstrated more remarkable anticancer, antimetastatic, and antiproliferative abilities in vitro , compared with those of free drugs. SOR@8P4 NPs showed high tumor targeting and significantly inhibited tumor growth in vivo . In summary, the drug delivery system of SOR@8P4 NPs provides new ideas for the clinical treatment of PCa.

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.

Androgen deprivation therapy has been used as a standard clinical treatment for prostate cancer, but the disease generally progresses to castration-resistant prostate cancer in a very short time. Enzalutamide (ENZ) is an emerging second-generation androgen receptor (AR) antagonist used for the treatment of patients with nonmetastatic castration-resistant prostate cancer (CRPC). However, due to the rapid onset of drug resistance, it provides only a modest increase in survival. Here, we propose a convenient and effective androgen receptor antagonist drug delivery strategy, that is, the use of a biocompatible nanoparticle (NP) drug delivery system for drug delivery to improve its bioavailability and therapeutic performance. Although the particle size of the phenylpropyl polymer (8P4) nanoparticles is small, it has a high drug-carrying capacity. ENZ-8P4 NPs can increase drug delivery efficiency, enhance drug cytotoxicity, and reduce the half-inhibitory concentration (IC50) of the drug. In addition, in vivo experiments confirmed that ENZ-8P4 preferentially accumulates in the tumor and significantly inhibits tumor growth. Hence, the 8P4 drug delivery system loaded with enzalutamide has excellent potential for the treatment of prostate cancer.