Complexation Nanoarchitectonics of Carbon Dots with Doxorubicin toward Photodynamic Anti-Cancer Therapy.

Carbon dots (Cdots) are known as photosensitizers in which the nitrogen doping is able to improve the oxygen-photosensitization performance and singlet-oxygen generation. Herein, the characteristics of nanoconjugates of nitrogen-doped Cdots and doxorubicin were compared with the property of nitrogen-doped Cdots alone. The investigation was performed for the evaluation of pH-dependent zeta potential, quantum yield, photosensitization efficiency and singlet-oxygen generation, besides spectroscopy (UV-visible absorption and fluorescence spectra) and cytotoxicity on cancer model (HeLa cells). Encapsulation efficiency, drug loading, and drug release without and with light irradiation were also carried out. These investigations were always pursued under the comparison among different nitrogen amounts (ethylenediamine/citric acid = 1-5) in Cdots, and some characteristics strongly depended on nitrogen amounts in Cdots. For instance, surface charge, UV-visible absorbance, emission intensity, quantum yield, photosensitization efficiency and singlet-oxygen generation were most effective at ethylenediamine/citric acid = 4. Moreover, strong conjugation of DOX to Cdots via π-π stacking and electrostatic interactions resulted in a high carrier efficiency and an effective drug loading and release. The results suggested that nitrogen-doped Cdots can be considered promising candidates to be used in a combination therapy involving photodynamic and anticancer strategies under the mutual effect with DOX.

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

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.

A nanocellulose-based platform towards targeted chemo-photodynamic/photothermal cancer therapy.

Cellulose nanocrystals (CNCs) have advantages as drug delivery carriers because of their biocompatibility and the presence of hydroxyl groups which favor chemical modification and drug binding. The present study describes the development of novel multifunctional rod-like CNCs-based carriers as therapeutic platforms: CNCs were hybridized with folic acid for actively targeting tumor cells, carbon dots (Cdots) for both imaging and photodynamic/photothermal treatments and doxorubicin (DOX) as an anticancer drug. Hybridized carriers displayed excellent drug-loading capacity. Moreover, Cdots-containing hybrids showed fluorescence and photosensitized singlet oxygen generation and photothermal behavior. Carriers exhibited pH-sensitive drug release because of changing interactions with DOX, and this release proved to be effective against in vitro cervical cancer cells, as evidenced by dose-dependent reduced cellular viabilities. Additionally, DOX release was promoted by light irradiation and the photodynamic behavior by reactive oxygen species was confirmed. These results demonstrate the potential of multifunctional CNCs-based carriers as platforms for multimodal photodynamic/photothermal-chemotherapy.