In this study, we aimed to develop anti-human epidermal growth factor receptor 2 (HER2) indocyanine green (ICG)-doxorubicin (DOX)-encapsulated polyethylene glycol-poly(lactic-co-glycolic acid) diblock copolymeric nanoparticles (HIDPPNPs) to explore the co-administration of phototherapy and chemotherapy for HER2-overexpressing breast cancer, a highly aggressive and medicine-resistant breast carcinoma. The HIDPPNPs were fabricated using a solvent evaporation technique followed by carbodiimide-mediated antibody conjugation on the nanoparticle surface. Compared with freely dissolved ICG, the HIDPPNPs conferred enhanced thermal stability to the entrapped ICG, were able to generate a hyperthermia effect at concentrations ≥1 μM ICG equivalent and provided increased production of singlet oxygen under 808-nm laser irradiation with an intensity of 6 W/cm². Furthermore, the uptake efficiency of the HIDPPNPs in MDA-MB-453/HER2(+) cells was approximately 2-fold higher than that in MCF7/HER2(−) cells, demonstrating that the HIDPPNPs specifically target HER2-expressing cells. Based on the viability analysis, the HIDPPNPs exhibited effective cytotoxicity upon light exposure (808 nm; 6 W/cm²), and the resulting cell death rate was even higher than that caused by using twice amount of encapsulated DOX or ICG alone. These results indicate that the developed HIDPPNPs may serve as a feasible tool for use in anti-HER2 breast cancer therapy with reduced chemotoxicity.

Diabetic foot ulcers remain one of the most difficult-to-treat complications of diabetes and may seriously threaten the life of patients since it frequently results in limb loss due to amputation, suggesting that an effective therapeutic strategy is still urgently needed. In this study, a chitosan-based heterogeneous composite hydrogel encapsulating perfluorocarbon emulsions, epidermal growth factor (EGF)-loaded chitosan nanoparticles, and polyhexamethylene biguanide (PHMB) named P_EE_NPPCH was developed for diabetic wound healing. The P_EE_NPPCH could sustainably release EGF and PHMB in an ion-rich environment to exert antibacterial effects and promote cell growth for wound repair. In addition, the P_EE_NPPCH can provide anti-inflammatory effects functioned by its main constituent of chitosan. Moreover, the P_EE_NPPCH can proactively offer oxygen delivery through the incorporation of perfluorocarbon and, therefore, is able to alleviate hypoxia conditions on diabetic wounds. These functionalities enabled a markedly enhanced wound healing efficacy on diabetic rats treated with the P_EE_NPPCHs, including thorough re-epithelization, a reduced inflammatory response, faster collagen deposition, and advanced collagen maturation resulting in a 95% of wound closure degree after 15 days that was 12.6% (p < 0.05) higher than the value of the group treated with the commercial dressing HeraDerm. Given the aforementioned advantages, together with the known merits of hydrogels, the developed P_EE_NPPCH is anticipated to be a feasible tool for clinical diabetic wound treatment.

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females worldwide. Among various types of breast cancer, the human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer is known to be more aggressive and often resistant to medicinal treatment, leading to an insufficient prognosis and poor susceptibility to chemotherapy and/or hormonal therapy in the current clinic. These circumstances implicate that developing an improved therapeutic strategy rather than persistently changing the anticancer drugs for trying is truly needed to successfully cure this type of breast cancer. In this study, we aimed to fabricate anti-HER2 indocyanine green (ICG)–doxorubicin (DOX)-loaded polyethyleneimine-coated perfluorocarbon double nanoemulsions (HIDPPDNEs) to explore the co-administration of phototherapy and chemotherapy for HER2-overexpressing breast cancer in vitro. The HIDPPDNE was first characterized as a sphere-like nanoparticle with surface charge of −57.1 ± 5.6 mV and size of 340.6 ± 4.5 nm, whereas the DOX release rates for the nanodroplets within 48 h in 4 and 37 °C were obtained by 8.13 ± 2.46% and 19.88 ± 2.75%, respectively. We then examined the target-ability of the nanostructure and found that the adhesion efficiency of the HIDPPDNEs onto HER2+ MDA-MB-453 cells was threefold higher than the nanodroplets without anti-HER2 antibody, indicating that the HIDPPDNEs are the product with HER2 binding specificity. In comparison to freely dissolved ICG, the HIDPPDNEs conferred an enhanced thermal stability to the entrapped ICG, and were able to provide a comparable hyperthermia effect and markedly increased production of singlet oxygen under near infrared irradiation (808 nm; 6 W/cm2). Based on the viability analyses, the results showed that the HIDPPDNEs were effective on cell eradication upon near infrared irradiation (808 nm; 6 W/cm2), and the resulting cell mortality was even higher than that caused by using twice amount of encapsulated DOX or ICG alone. This work demonstrates that the HIDPPDNEs are able to provide improved ICG stability, binding specificity, and enhanced anticancer efficacy as compared to equal dosage of free ICG and/or DOX, showing a high potential for use in HER2 breast cancer therapy with reduced chemotoxicity.