Smart composite scaffold to synchronize magnetic hyperthermia and chemotherapy for efficient breast cancer therapy.

Combination of different therapies is an attractive approach for cancer therapy. However, it is a challenge to synchronize different therapies for maximization of therapeutic effects. In this work, a smart composite scaffold that could synchronize magnetic hyperthermia and chemotherapy was prepared by hybridization of magnetic Fe3O4 nanoparticles and doxorubicin (Dox)-loaded thermosensitive liposomes with biodegradable polymers. Irradiation of alternating magnetic field (AMF) could not only increase the scaffold temperature for magnetic hyperthermia but also trigger the release of Dox for chemotherapy. The two functions of magnetic hyperthermia and chemotherapy were synchronized by switching AMF on and off. The synergistic anticancer effects of the composite scaffold were confirmed by in vitro cell culture and in vivo animal experiments. The composite scaffold could efficiently eliminate breast cancer cells under AMF irradiation. Moreover, the scaffold could support proliferation and adipogenic differentiation of mesenchymal stem cells for adipose tissue reconstruction after anticancer treatment. In vivo regeneration experiments showed that the composite scaffolds could effectively maintain their structural integrity and facilitate the infiltration and proliferation of normal cells within the scaffolds. The composite scaffold possesses multi-functions and is attractive as a novel platform for efficient breast cancer therapy.

Composite Scaffolds of Gelatin and Fe3 O4 Nanoparticles for Magnetic Hyperthermia-Based Breast Cancer Treatment and Adipose Tissue Regeneration.

Postsurgical treatment of breast cancer remains a challenge with regard to killing residual cancer cells and regenerating breast defects. To prepare composite scaffolds for postoperative use, gelatin is chemically modified with folic acid (FA) and used for hybridization with citrate-modified Fe3 O4 nanoparticles (Fe3 O4 -citrate NPs) to fabricate Fe3 O4 /gelatin composite scaffolds which pore structures are controlled by free ice microparticles. The composite scaffolds have large spherical pores that are interconnected to facilitate cell entry and exit. The FA-functionalized composite scaffolds have the ability to capture breast cancer cells. The Fe3 O4 /gelatin composite scaffolds possess a high capacity for magnetic-thermal conversion to ablate breast cancer cells during alternating magnetic field (AMF) irradiation. In addition, the composite scaffolds facilitate the growth and adipogenesis of mesenchymal stem cells. The composite scaffolds have multiple functions for eradication of residual cancer cells under AMF irradiation and for regeneration of resected adipose tissue when AMF is off.

Stepwise photothermal therapy and chemotherapy by composite scaffolds of gold nanoparticles, BP nanosheets and gelatin immobilized with doxorubicin-loaded thermosensitive liposomes.

In recent years, the synergistic effect of photothermal therapy (PTT) and chemotherapy has been recognized as an effective strategy for cancer treatment. Controlling the PTT temperature and drug release profile is desirable for minimizing the unexpected damage to normal cells. In this study, a smart platform of stepwise PTT and chemotherapy has been developed by using composite porous scaffolds of biodegradable black phosphorus (BP) nanosheets, gold nanorods(AuNRs), doxorubicin (Dox)-encapsulated thermosensitive liposomes and biodegradable polymers. Under near-infrared (NIR) laser irradiation, the composite scaffolds could attain high and low local temperatures before and after BP degradation, respectively. Dox release from the composite scaffolds could be controlled by the temperature change. In vitro cell culture and in vivo animal experiments indicated that a strong synergistic effect of PTT and chemotherapy could be achieved at an early stage of treatment before BP degradation, and a mild hyperthermia effect was shown for chemotherapy in the late stage after BP degradation. Moreover, the composite scaffolds after the complete release of Dox could support the proliferation of mesenchymal stem cells. The composite scaffolds showed a synergistic effect of stepwise PTT and chemotherapy for breast cancer elimination and promoted stem cell activities after killing cancer cells.

Preparation of composite scaffolds composed of gelatin and Au nanostar-deposited black phosphorus nanosheets for the photothermal ablation of cancer cells and adipogenic differentiation of stem cells.

Photothermal nanoparticles are important in photothermal therapy. Combining different nanoparticles can achieve a high photothermal capacity. In this study, composite nanoparticles composed of black phosphorus nanosheets (BPNSs) and gold nanostars (BP-AuNSs) were synthesized by using BPNSs as the reductant. AuNSs were deposited on the BPNSs. The BP-AuNSs were further hybridized with porous gelatin scaffolds to prepare gelatin-BP-AuNS composite scaffolds. The gelatin-BP-AuNS composite scaffolds promoted cell migration and distribution. The synergistic effects of the BPNSs and AuNSs endowed the gelatin-BP-AuNS composite scaffolds with excellent photothermal properties. The gelatin-BP-AuNS composite scaffolds eliminated cancer cells after near infrared laser exposure and supported the adipogenic differentiation of human mesenchymal stem cells. Thus, this gelatin-BP-AuNS composite scaffold holds promise for breast cancer therapy.

Near-Infrared Light Irradiation of Porphyrin-Modified Gold Nanoparticles Promotes Cancer-Cell-Specific Cytotoxicity.

The use of nanoparticles has been investigated as a new cancer treatment. These can induce specific cytotoxicity in cancer cells. In particular, Au nanoparticles (AuNPs) have unique characteristics. The maximum absorption spectrum of AuNPs can be adjusted to modify their size or shape to absorb near-infrared light that can penetrate into tissue without photodamage. Thus, the combination of AuNPs and near-infrared light can be used to treat cancer in deep-seated organs. To obtain effective cancer-specific accumulation of AuNPs, we focused on porphyrin and synthesized a porphyrin-attached Au compound: Au-HpD. In this study, we investigated whether Au-HpD possesses cancer-specific accumulation and cytotoxicity. Intracellular Au-HpD accumulation was higher in cancer cells than in normal cells. In order to analyze the cytotoxicity induced by Au-HpD, cancer cells and normal cells were co-cultured in the presence of Au-HpD; then, they were subjected to 870 nm laser irradiation. We observed that, after laser irradiation, cancer cells showed significant morphological changes, such as chromatin condensation and nuclear fragmentation indicative of cell apoptosis. This strong effect was not observed when normal cells were irradiated. Moreover, cancer cells underwent cell apoptosis with combination therapy.

PLGA-collagen-BPNS Bifunctional composite mesh for photothermal therapy of melanoma and skin tissue engineering.

The treatment of melanoma requires not only the elimination of skin cancer cells but also skin regeneration to heal defects. To achieve this goal, a bifunctional composite scaffold of poly(DL-lactic-co-glycolic acid) (PLGA), collagen and black phosphorus nanosheets (BPNSs) was prepared by hybridizing a BPNS-embedded collagen sponge with a PLGA knitted mesh. The composite mesh increased the temperature under near-infrared laser irradiation. The incorporation of BPNSs provided the PLGA-collagen-BPNS composite mesh with excellent photothermal properties for the photothermal ablation of melanoma cells both in vitro and in vivo. The PLGA-collagen-BPNS composite mesh had high mechanical strength for easy handling. The PLGA-collagen-BPNS composite mesh facilitated the proliferation of fibroblasts, promoted the expression of angiogenesis-related genes and the genes of components of the extracellular matrix for skin tissue regeneration. The high mechanical strength, photothermal ablation capability and skin tissue regeneration effects demonstrate that the bifunctional PLGA-collagen-BPNS composite mesh is a versatile and effective platform for the treatment of melanoma and the regeneration of skin defects.

Composite scaffolds of black phosphorus nanosheets and gelatin with controlled pore structures for photothermal cancer therapy and adipose tissue engineering.

Breast cancer treatment needs to eradicate cancer cells and restore breast defects after surgical intervention. Herein, bifunctional composite scaffolds of black phosphorus nanosheets (BPNSs) and gelatin were designed to kill breast cancer cells and induce adipose tissue reconstruction. The composite scaffolds were prepared by hybridizing photothermal BPNSs with porous gelatin matrices by adding pre-prepared ice particles to precisely adjust their pore structures. The composite scaffolds had large, well-interconnected spherical pores, which allowed cell migration and infiltration. Hybridization with BPNSs increased the compression strength of the scaffolds. The composite scaffolds possessed a high photothermal conversion capacity that was dependent on the amount of BPNSs. The composite scaffold with a high amount of BPNSs could completely kill breast cancer cells in vitro and in vivo under laser irradiation. Moreover, cell culture and animal experiment results showed that the composite scaffolds promoted lipid oil droplet formation and upregulated the expression of adipogenesis-related genes when hMSCs were cultured in the scaffolds. The composite scaffolds could offer a facile platform to exert anticancer effects against breast cancer cells and promote the reconstruction of adipose tissue.

Redox nanoparticles inhibit curcumin oxidative degradation and enhance its therapeutic effect on prostate cancer.

Curcumin is a phytochemical with diverse molecular targets and is well known for its anti-tumor potential. However, it has limited application in cancer therapy because curcumin undergoes rapid oxidative degradation at physiological conditions resulting in poor stability and bio-availability. In this study, we were able to suppress curcumin's oxidative degradation by encapsulating it in a nanoparticle that also acts as a radical scavenger. We prepared curcumin-loaded pH-sensitive redox nanoparticles (RNP(N)) by self-assembling amphiphilic block copolymers conjugated with reactive oxygen species (ROS) scavenging nitroxide radicals to ensure the delivery of minimally degraded curcumin to target regions. In vitro analysis confirmed that the entrapment of both curcumin and nitroxide radicals in the hydrophobic core of RNP(N) suppressed curcumin degradation in conditions mimicking the physiological environment. Evaluation of apoptosis-related molecules in the cells, such as ceramides, caspases, apoptosis-inducing factor, and acid ceramidase revealed that curcumin loaded RNP(N) induced strong apoptosis compared to free curcumin. Lastly, intravenous injection of curcumin loaded RNP(N) suppressed tumor growth in vivo, which is due to the increased bio-availability and significant ROS scavenging at tumor sites. These results demonstrated that RNP(N) is a promising drug carrier with unique ROS-scavenging abilities, and it is able to overcome the crucial hurdle of curcumin's limitations to enhance its therapeutic potential.