Nanoscaled PAMAM Dendrimer Spacer Improved the Photothermal‒Photodynamic Treatment Efficiency of Photosensitizer‐Decorated Confeito‐Like Gold Nanoparticles for Cancer Therapy

• Published in: Macromolecular bioscience 2022-08, Vol.22 (8), p.e2200130-n/a
• Main Authors: Saw, Wen Shang, Anasamy, Theebaa, Do, Thu Thi Anh, Lee, Hong Boon, Chee, Chin Fei, Isci, Umit, Misran, Misni, Dumoulin, Fabienne, Chong, Wu Yi, Kiew, Lik Voon, Imae, Toyoko, Chung, Lip Yong
• Format: Article
• Language: English
• Subjects: Anticancer properties; Antitumor activity; Biocompatibility; Breast cancer; Cancer; Cancer therapies; dendrimer; Effectiveness; Gold; gold nanoparticles; Heat generation; Hybrid systems; In vivo methods and tests; Internalization; Irradiation; Nanoparticles; Oxygen; Photodynamic therapy; Photosensitization; photothermal‒photodynamic therapy; Phototoxicity; phthalocyanines; plasmon enhancement; Porphyrins; Singlet oxygen; spacer; Tumor cell lines; Tumors
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.202200130

A critical factor in developing an efficient photosensitizer‐gold nanoparticle (PS‐AuNP) hybrid system with improved plasmonic photosensitization is to allocate a suitable space between AuNPs and PS. Poly(amidoamine) (PAMAM) dendrimer is selected as a spacer between the PS and confeito‐like gold nanoparticles (confeito‐AuNPs), providing the required distance (≈2.5‒22.5 nm) for plasmon‐enhanced singlet oxygen generation and heat production upon 638‐nm laser irradiation and increase the cellular internalization of the nanoconjugates. The loading of the PS, tetrakis(4‐carboxyphenyl) porphyrin (TCPP), and modified zinc phthalocyanine (ZnPc1) onto PAMAM‐confeito‐AuNPs demonstrate better in vitro cancer cell‐killing efficacy, as the combined photothermal‒photodynamic therapies (PTT‒PDTs) outperforms the single treatment modalities (PTT or PDT alone). These PS‐PAMAM‐confeito‐AuNPs also demonstrate higher phototoxicity than photosensitizers directly conjugated to confeito‐AuNPs (TCPP‐confeito‐AuNPs and ZnPc1‐confeito‐AuNPs) against all breast cancer cell lines tested (MDA‐MB‐231, MCF7, and 4T1). In the in vivo studies, TCPP‐PAMAM‐confeito‐AuNPs are biocompatible and exhibit a selective tumor accumulation effect, resulting in higher antitumor efficacy than free TCPP, PAMAM‐confeito‐AuNPs, and TCPP‐confeito‐AuNPs. In vitro and in vivo evaluations confirm PAMAM effectiveness in facilitating cellular uptake, plasmon‐enhanced singlet oxygen and heat generation. In summary, this study highlights the potential of integrating a PAMAM spacer in enhancing the plasmon effect‐based photothermal‒photodynamic anticancer treatment efficiency of PS‐decorated confeito‐AuNPs. It is vital to allocate a suitable distance between photothermal and photodynamic therapeutic agents to create the plasmonic photosensitization effect. Poly(amidoamine) dendrimer adoption as a spacer between the photosensitizers and the confeito‐like gold nanoparticles provides the required distance for plasmon‐enhanced singlet oxygen generation and heat production, resulting in the improvement of both in vitro and in vivo therapeutic efficacies.