Yamin Yang

Gold Nanoparticle-Enhanced and Size-Dependent Generation of Reactive Oxygen Species from Protoporphyrin IX

Photosensitizer, protoporphyrin IX (PpIX), was conjugated with Au nanoparticles (Au NPs) of 19, 66, and 106 nm diameter to study the size-dependent enhancement of reactive oxygen species (ROS) formation enabled by Au NPs. The ROS enhancement ratio is determined to be 1:2.56:4.72 in order of increasing Au NP size, in general agreement with theoretically calculated field enhancement to the fourth power. The convergence of the experimental and simulated results suggests that Au NP-enhanced and size-dependent ROS formation can be attributed directly to the localized electromagnetic field as a result of surface plasmonic resonance of Au NPs under light irradiation. In vitro study on the ROS formation enabled by PpIX-conjugated Au NPs in human breast cancer cells (MDA-MB-231) revealed the similar size-dependent enhancement of intracellular ROS formation, while the enhancement greatly depended on cellular uptake of Au NPs. Cellular photodynamic therapy revealed that cell destruction significantly increased in the presence of Au NPs. Compared to the untreated control (0% destruction), 22.6% cell destruction was seen in the PpIX alone group and more than 50% cell destruction was obtained for all PpIX-conjugated Au NPs. The 66 nm Au NPs yielded the highest cell destruction, consistent with the highest cellular uptake and highest ROS formation. Clearly, the complex cellular environment, size-dependent cellular uptake of Au NPs, and ROS generations are vital contributors to the overall cellular PDT efficacy.

Synergistic Integration of Layer-by-Layer Assembly of Photosensitizer and Gold Nanorings for Enhanced Photodynamic Therapy in the Near Infrared

A layer-by-layer (LbL) assembly strategy was used to incorporate high concentrations of Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) photosensitizer (PS) onto plasmonic Au nanorings (Au NRs) for increasing the cellular uptake of AlPcS4 and subsequently enhancing the efficacy of photodynamic therapy (PDT) of human breast cancer cells (MDA-MB-231) in the near-infrared (NIR) range. Au NRs with two layers of AlPcS4 (Au NR/(AlPcS4)2) markedly increased the cellular internalization of AlPcS4 and elevated the generation of reactive oxygen species (ROS). Quenching the photosensitivity of AlPcS4 on the Au NR surface during the uptake and then significant ROS formation only upon PS release inside the cellular compartment made it possible to achieve a high PDT specificity and efficacy. PDT of breast cancer cells following 4 h of incubation with various formula revealed the following cell destruction rate: ∼10% with free AlPcS4, ∼23% with singly layered Au NR/(AlPcS4)1 complex, and ∼50% with doubly layered Au NR/(AlPcS4)2. Incubation with Au NR/(AlPcS4)2 for an additional 2 h resulted in ∼85% cell killing, more than 8-fold increase compared to AlPcS4 alone. Together, integration of LbL of PS with Au NRs holds a significant promise for PDT therapeutic treatment of a variety of cancers.

Gold nanoparticle-enhanced photodynamic therapy: effects of surface charge and mitochondrial targeting

AIM The authors aimed to further improve the efficiency and selectivity of gold nanoparticle (Au NP)-assisted photodynamic therapy by modulating the surface charge of Au NPs and delivering Au NPs particularly to mitochondria of breast cancer cells. METHODS Solid gold nanospheres (˜50 nm) with negative and positive surface charge were synthesized respectively, and mitochondria-targeting Au NPs were prepared by conjugating with triphenylphosphonium molecules. CONCLUSION Positively charged Au NPs were preferably taken up by breast cancer cells. Combination of positive surface charge with mitochondria-targeting domain onto Au NPs allowed their accumulation in the mitochondria of breast cancer cells to significantly elevate reactive oxygen species formation in 5-aminolevulinic-acid-enabled photodynamic therapy and improve selective destruction of breast cancer cells.

Perspectives of Nanotechnology in Minimally Invasive Therapy of Breast Cancer

Breast cancer, the most common type of cancer among women in the western world, affects approximately one out of every eight women over their lifetime. In recognition of the high invasiveness of surgical excision and severe side effects of chemical and radiation therapies, increasing efforts are made to seek minimally invasive modalities with fewer side effects. Nanoparticles (<100 nm in size) have shown promising capabilities for delivering targeted therapeutic drugs to cancer cells and confining the treatment mainly within tumors. Additionally, some nanoparticles exhibit distinct properties, such as conversion of photonic energy into heat, and these properties enable eradication of cancer cells. In this review, current utilization of nanostructures for cancer therapy, especially in minimally invasive therapy, is summarized with a particular interest in breast cancer.

Strategies in the design of gold nanoparticles for intracellular targeting: opportunities and challenges

With unique physicochemical properties, gold nanoparticles (Au NPs) have demonstrated their potential as drug carriers or therapeutic agents. Effective guidance of Au NPs into specific intracellular destinations becomes increasingly important as we strive to further improve the efficiency of drug delivery and modulate controllable cellular responses. In this review, we summarized recent advances in designing Au NPs with the capabilities of cellular penetration and internalization, endosomal escape, intracellular trafficking and subcellular localization via various approaches including physical injection, tuning the physiochemical parameters of Au NPs, and surface modification with targeting ligands. Strategies for delivering Au NPs to specific subcellular destinations including the nucleus, mitochondria, endoplasmic reticulum, lysosomes are also discussed. Moreover, current challenges associated with intracellular targeting of Au NPs are discussed with future perspectives proposed.

Targeting Antitumor Immune Response for Enhancing the Efficacy of Photodynamic Therapy of Cancer: Recent Advances and Future Perspectives.

Photodynamic therapy (PDT) is a minimally invasive therapeutic strategy for cancer treatment, which can destroy local tumor cells and induce systemic antitumor immune response, whereas, focusing on improving direct cytotoxicity to tumor cells treated by PDT, there is growing interest in developing approaches to further explore the immune stimulatory properties of PDT. In this review we summarize the current knowledge of the innate and adaptive immune responses induced by PDT against tumors, providing evidence showing PDT facilitated-antitumor immunity. Various immunotherapeutic approaches on different cells are reviewed for their effectiveness in improving the treatment efficiency in concert with PDT. Future perspectives are discussed for further enhancing PDT efficiency via intracellular targetable drug delivery as well as optimized experimental model development associated with the study of antitumor immune response.

Gold nanoring-enhanced generation of singlet oxygen: an intricate correlation with surface plasmon resonance and polyelectrolyte bilayers

We report the dependence of gold nanoring (Au NR)-enhanced singlet oxygen (1O2) generation on localized surface plasmon resonance (LSPR) wavelength and separation distance between Au NR and photosensitizers. Using Au NR of tunable LSPR and poly(styrene sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) bilayers via layer-by-layer (LbL) assembly on Au NR as molecular spacers, we found that 1O2 generation from Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) conjugated on the Au NR can be optimized through proper combination of LSPR and the separation distance. More importantly, 1O2 enhancement follows a different correlation with the separation distance compared to that of AlPcS4 fluorescence enhancement. Our experimental findings are consistent with the prediction by boundary element method (BEM) calculations. Our study paves the way to the design of LSPR-enhanced 1O2 generation for improved efficacy of photodynamic therapy of cancers.

Colloidal gold nanorings for improved photodynamic therapy through field-enhanced generation of reactive oxygen species

Au nanostructures that exhibit strong localized surface plasmon resonance (SPR) have excellent potential for photo-medicine, among a host of other applications. Here, we report the synthesis and use of colloidal gold nanorings (GNRs) with potential for enhanced photodynamic therapy of cancer. The GNRs were fabricated via galvanic replacement reaction of sacrificial Co nanoparticles in gold salt solution with low molecular weight (Mw = 2,500) poly(vinylpyrrolidone) (PVP) as a stabilizing agent. The size and the opening of the GNRs were controlled by the size of the starting Co particles and the concentration of the gold salt. UV-Vis absorption measurements indicated the tunability of the SPR of the GNRs from 560 nm to 780 nm. MTT assay showed that GNRs were non-toxic and biocompatible when incubated with breast cancer cells as well as the healthy counterpart cells. GNRs conjugated with 5-aminolevulinic acid (5-ALA) photosensitizer precursor led to elevated formation of reactive oxygen species and improved efficacy of photodynamic therapy of breast cancer cells under light irradiation compared to 5-ALA alone. These results can be attributed to significantly enhance localized electromagnetic field of the GNRs.

Colloidal plasmonic gold nanoparticles and gold nanorings: shape-dependent generation of singlet oxygen and their performance in enhanced photodynamic cancer therapy

Introduction In recognition of the potentials of gold nanoparticles (Au NPs) in enhanced photodynamic therapy (PDT) for cancer, it is desirable to further understand the shape-dependent surface plasmonic resonance (SPR) properties of various gold nanostructures and evaluate their performances in PDT. Materials and methods Monodispersed colloidal spherical solid Au NPs were synthesized by UV-assisted reduction using chloroauric acid and sodium citrate, and hollow gold nanorings (Au NRs) with similar outer diameter were synthesized based on sacrificial galvanic replacement method. The enhanced electromagnetic (EM) field distribution and their corresponding efficiency in enhancing singlet oxygen (1O2) generation of both gold nanostructures were investigated based on theoretical simulation and experimental measurements. Their shape-dependent SPR response and resulted cell destruction during cellular PDT in combination with 5-aminolevulinic acid (5-ALA) were further studied under different irradiation conditions. Results With comparable cellular uptake, more elevated formation of 1O2 in 5-ALA-enabled PDT was detected with the presence of Au NRs than that with Au NPs under broadband light irradiation in both cell-free and intracellular conditions. As a result of the unique morphological attributes, exhibiting plasmonic effect of Au NRs was still achievable in the near infrared (NIR) region, which led to an enhanced therapeutic efficacy of PDT under NIR light irradiation. Conclusion Shape-dependent SPR response of colloidal Au NPs and Au NRs and their respective effects in promoting PDT efficiency were demonstrated in present study. Our innovative colloidal Au NRs with interior region accessible to surrounding photosensitizers would serve as efficient enhancers of PDT potentially for deep tumor treatment.