Photoacoustic (PA)/near-infrared fluorescence (NIRF) dual-modal imaging-guided phototherapy has been wide explored very recently. However, the development of high-efficiency and simplified-performed theranostic system for amplifying imaging-guided photothermal therapy/photodynamic therapy (PTT/PDT) is still a great challenge. Herein, a single-light-triggered indocyanine green (ICG)-loaded PEGylation silver nanoparticle core/polyaniline shell (Ag@PANI) nanocomposites (ICG-Ag@PANI) for PA/NIRF imaging-guided enhanced PTT/PDT synergistic effect has been successfully constructed. In this study, the synthesized Ag@PANI nanocomposites are utilized not only as the promising photothermal agent but also as potential nanovehicles for loading photosensitizer ICG via π–π stacking and hydrophobic interaction. The as-prepared ICG-Ag@PANI possesses many superior properties such as strong optical absorption in the near-infrared (NIR) region, enhanced photostability of ICG, as well as outstanding NIR laser-induced local hyperthermia and reactive oxygen species (ROS) generation. In the in vivo study, PA/NIRF dual-modal imaging confirms the accumulation and distribution of ICG-Ag@PANI in the tumor region via enhanced permeability and retention (EPR) effect. Moreover, the PTT effect of ICG-Ag@PANI rapidly raised the tumor temperature to 56.8 °C within 5 min. It is also demonstrated that the cytotoxic ROS generation ability of ICG is well maintained after being loaded onto Ag@PANI nanocomposites. Remarkably, in comparison with PTT or PDT alone, the single 808 nm NIR laser-triggered combined PTT/PDT therapy exhibits enhanced HeLa cells lethality in vitro and tumor growth inhibition in vivo.Keywords: Ag@PANI nanocomposites; dual-imaging-guided; ICG; PTT/PDT; single-light-triggered; theranostic system;

In this study, we introduce a versatile nanomaterial based on MoS2 quantum dot@polyaniline (MoS2@PANI) inorganic–organic nanohybrids, which exhibit good potential to not only enhance photoaccoustic (PA) imaging/X-ray computed tomography (CT) signal but also perform efficient radiotherapy (RT)/photothermal therapy (PTT) of cancer. Upon the intravenous injection of MoS2@PANI hybrid nanoparticles, the in vivo tumor could be precisely positioned and thoroughly eliminated under the PA/CT image-guided combination therapy of PTT/RT. This versatile nanohybrid could show good potential to facilitate simultaneously dual-modal imaging and synergetic PTT/RT to realize better anticancer efficiency.Keywords: dual-modal CT/photoacoustic imaging; inorganic−organic nanohybrids; MoS2 quantum dots; photothermal/radiation therapy; polyaniline

This work was devoted to the development of a lipid-based theranostic nanoparticle able to simultaneously host conjugated polymer dots, doxorubicin (Dox) and folate acid (FA). Poly(9,9-dioctylfluorene-2,7-diyl-co-benzothiadiazole) (PFBT) was chosen as the fluorescent probe because of its high brightness in in vitro cellular uptake studies and good biocompatibility in in vitro/in vivo toxicity experiments. The theranostic liposomes (PFBT–Dox–Lip–FA) exhibited a hydrodynamic size of 127.30 ± 3.20 (nm) with a zeta potential of −25.00 ± 2.00 (mV). Mostly importantly, the extent of Dox release at 24 h from PFBT–Dox–Lip–FA showed a satisfactory result under mild hyperthermia conditions compared with Dox–Lip–FA. Such rapid release led to a lower half maximal inhibitory concentration (IC50) in MCF-7 cells at 16.8 ± 4.5 (μg mL−1), whereas the IC50 of Dox–Lip–FA (37 °C) was 28.3 ± 3.7 (μg mL−1). The cellular uptake study also revealed higher drug accumulation in tumor cells for theranostic liposomes. In vivo studies of PFBT–Dox–Lip–FA on tumor-bearing mouse models revealed that the distribution of liposomes in the tumors could be indicated accurately by PFBT. Besides, tumor-bearing mice could be significantly inhibited by PFBT–Dox–Lip–FA. Together with its negligible in vivo toxicity, PFBT–Dox–Lip–FA is a useful system for simultaneous cancer diagnosis and targeted drug delivery.

The applications of photodynamic therapy (PDT) are usually limited by the low tumor selectivity of photosensitizers. Herein, we report a near infrared (NIR) imaging multifunctional nanocarrier, so called “theranosome (TNS)”, which encapsulated both chlorin e6 (Ce6, photosensitizer) and IR780 iodide (IR780, photothermal and NIR imaging agent) to realize enhanced PDT efficacy. The phototoxicity of Ce6 was effectively restrained by IR780. Upon NIR laser irradiation at 808 nm, IR780 in the TNS could be degraded, while the phototoxicity of Ce6 could be recovered. In addition, we proved that attaching a triphenylphosphonium (TPP) group to the TNS (TPP-IR780/Ce6-TNS) could greatly facilitate its mitochondrial targeting ability so as to offer a remarkably improved PDT efficacy. This newly constructed TNS exhibited high toxicity to the tumor cells in vitro, indicating TNS was a promising nanocarrier used as a PTT combined activatable PDT.

The development of treatment protocols that results in a complete response to chemotherapy has been hampered by low efficacy and systemic toxicity. Here, we created a pH sensitive copper–doxorubicin complex within the core of temperature-sensitive liposomes to maintain the stability during blood circulation and trigger Dox release in the tumor site. Synergistically, we also rationally applied gold nanorods (AuNRs) coupled with near-infrared (NIR) field strength to produce a precise and localized temperature, which not only remotely controlled the drug release but also directly destroyed the tumor, to enhance the therapeutic efficacy. As expected, the in vitro release studies showed that the drug release from CuDox-TSLs (Copper ion mediated Doxorubicin loading-Temperature Sensitive Liposomes) was both pH-dependent and temperature-dependent. Furthermore, MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assays showed that CuDox-TSLs combined with AuNRs exhibited a closer antiproliferative activity to free Dox in MCF-7 cells. The efficient intracellular Dox release from CuDox-TSLs toward the tumor cells further confirmed the anti-tumor effect. Moreover, the in vivo imaging and biodistribution studies revealed that CuDox-TSLs combined with AuNRs could actively target the tumor site. In addition, the therapeutic studies in MCF-7 nude mice exhibited CuDox-TSLs plus AuNRs in combination with NIR irradiation inhibited tumor growth to a great extent and possessed much lower side effects, which were further confirmed by systemic histological analyses. All detailed evidence suggested a considerable potential of CuDox-TSLs combined with AuNRs for treatment of metastatic cancer.

The therapeutic effectiveness of chemotherapy was hampered by dose-limiting toxicity and was optimal only when tumor cells were subjected to a maximum drug exposure. The purpose of this work was to design a dual-functional thermosensitive bubble-generating liposome (BTSL) combined with conjugated targeted ligand (folate, FA) and photothermal agent (IR780), to realize enhanced therapeutic and diagnostic functions. This drug carrier was proposed to target tumor cells owing to FA-specific binding, followed by triggering drug release due to the decomposition of encapsulated ammonium bicarbonate (NH4HCO3) (generated CO2 bubbles) by being subjected to near-infrared (near-IR) laser irradiation, creating permeable defects in the lipid bilayer that rapidly release drug. In vitro temperature-triggered release study indicated the BTSL system was sensitive to heat triggering, resulting in rapid drug release under hyperthermia. For in vitro cellular uptake experiments, different results were observed on human epidermoid carcinoma cells (KB cells) and human lung cancer cells (A549 cells) due to their different (positive or negative) response to FA receptor. Furthermore, in vivo biodistribution analysis and antitumor study indicated IR780-BTSL-FA could specifically target KB tumor cells, exhibiting longer circulation time than free drug. In the pharmacodynamics experiments, IR780-BTSL-FA efficiently inhibited tumor growth in nude mice with no evident side effect to normal tissues and organs. Results of this study demonstrated that the constructed smart theranostic nanocarrier IR780-BTSL-FA might contribute to establishment of tumor-selective and effective chemotherapy.Keywords: bubble thermosensitive liposomes; doxorubicin; folate-receptor targeted; hyperthermia-mediated; IR780; tumor chemotherapy

Novel photoinduced triple-response antitumor therapeutic system based on hollow gold nanospheres (HAuNS), pH (low) insertion peptide (pHLIP), and Chlorin e6 (Ce6), was reported for the first time. The system was able to intracellularly deliver the nanocarriers by the transmembrane ability of pHLIP at the condition of pH 6.2. Ce6 and pHLIP were then released from the surface of the carriers due to the weakening electrostatic interaction with HAuNS under the photoirradiation. Herein, HAuNS performed two different functions: (1) as a nanocarrier because of the excellent loading capability; (2) experienced the photothermal therapy (PTT) effect as a photothermal coupling agent (PTCA), thus enhancing the photodynamic therapy (PDT) effect of Ce6.Keywords: one-step PTT/PDT effect; pH-driven targeting; phototriggered release; single-light inducement; triple response

The primary challenge of cancer therapy was the failure of most chemotherapeutics to accumulate in the tumors, additionally causing serious systemic side effects. We designed a tumor-targeting accumulated and locally triggered-release nanocarrier system to increase the intratumoral drug concentration and thus the efficacy of chemotherapy, based on gold nanorods (GNRs) and thermosensitive liposomes (TSLs). PEGylated GNRs could not only make nanocarriers to co-accumulate in tumors depending on enhanced permeability and retention (EPR) effect, but also generated heat locally under near-infrared (NIR) stimulation. CO2 bubbles were generated by the encapsulated ammonium bicarbonate (ABC) under hyperthermia, thus the co-encapsulated drug was released and local drug concentration was increased along with the disintegration of liposomal membrane. On the other hand, this dual-targeting system prevented the drug leakage in blood circulation or other organs while facilitated most of the active agents delivered to tumors. In vitro and in vivo experiments revealed high cytotoxicity and good affinity of HTSL to MDA-MB-435 cells when used synergistically with GNRs, but low toxicity to normal cells at the same condition. When combined with thermotherapy, the smart nanocarrier system held significant promise for future cancer treatment for their markedly improved therapeutic efficacy and decreased systemic toxicity.

The present study aimed to develop and optimize a microemulsion (ME) nanocarrier system as a topical vehicle for azelaic acid (AZA) to improve its skin location and therapeutic efficacy. A D-optimal mixture experimental design was utilized to optimize ME for realizing maximum skin retention and appropriate droplet size. Three formulation variables, Smix X1 (a mixture of Span 20/ethanol, 1:9, w/w), water X2 and Oil X3 (Capryol 90), were included in the design, while the three responses were skin retention (Y1), amount of AZA in collection medium after 24 h (Y2) and mean particle size (Y3). The values of the formulation components (X1, X2 and X3) were 50.3%, 13.5% and 36.2%, respectively. In in vitro studies, the optimal ME revealed a much higher release rate, and enhanced skin targeting and penetration effects of AZA relative to control formulations (ethanol solution based gel and commercial cream). An attenuated total reflectance Fourier-transform infrared spectroscopy study further confirmed to us that the vehicles could transport the active agents across the stratum corneum (SC) layer by changing the amount and arrangement of lipid within the SC. In addition, a skin irritation test and pharmacodynamics studies were conducted, and the results suggested that the optimal ME exhibited a prominent therapeutic effect compared to control formulations, without any irritant response.

The present study was aimed at the encapsulation of ketoconazole (KCZ) in the novel modified nanovesicles for dermal targeting delivery. To this purpose, innovative modified vesicles were prepared with soy phospholipid and aqueous solutions containing different concentrations of two targeting modifiers, 1,2-hexanediol and 1,4-cyclohexanediol. Conventional liposomes, with soy phospholipid and cholesterol, were used as control. The prepared formulations were characterized in terms of entrapment efficiency, size distribution, morphology, and stability. Dermal KCZ targeting delivery from modified vesicles was investigated in vitro and in vivo through newborn pig and rat skin, respectively. All vesicles showed a mean size ranging from 58 to 147 nm with fairly narrow size distribution and drug entrapment efficiency between 20 and 75 %. Results of in vitro and in vivo studies indicated that modified vesicles provided an improved KCZ targeting delivery into skin layers. Images of the confocal laser scanning microscopy analyses supported the conclusion that modified vesicles could enhance the drug deposition into the skin strata and reduce the drug permeation into the blood, due to a synergic effect of phospholipid and modifiers. Finally, histological evaluation showed that KCZ-loaded modified vesicles caused no irritation to the skin. The results obtained encouraged the use of the KCZ-loaded modified vesicles as the formulation for the potential topical treatment of fungal infections.

Rod-shape nanocarriers have attracted great interest because of their better cell internalization capacity and higher drug loading properties. Besides, the combination of photodynamic therapy (PDT) and photothermal therapy (PTT) holds great promise to overcome respective limitations of the anti-cancer treatment. In this work, we first report Au nanorods-capped and Ce6-doped mesoporous silica nanorods (AuNRs-Ce6-MSNRs) for the single wavelength of near infrared (NIR) light triggered combined phototherapy. AuNRs-Ce6-MSNRs are not only able to generate hyperthermia to perform PTT effect based on the AuNRs, but also can produce singlet oxygen (1O2) for PDT effect based on Ce6 after uncapping of AuNRs under the single NIR wavelength irradiation. In addition, the combined therapy can be dual-imaging guided by taking the photoacoustic (PA) and NIR fluorescence (NIRF) imaging of AuNRs and Ce6, respectively. What's more, by utilizing the special structure of MSNRs, this nanocarrier can serve as a drug delivery platform with high drug loading capacity and enhanced cellular uptake efficiency. The multi-functional nanocomposite is designed to integrate photothermal and photodynamic therapy, in vivo dual-imaging into one system, achieving synergistic anti-tumor effects both in vitro and in vivo.

The objective of this study is to investigate the effect of 1,4-cyclohexanediol as a retardant on the percutaneous absorption and penetration of azelaic acid. Hairless rat skin was mounted on Franz diffusion cells and treated with topical formulations containing solubilized azelaic acid with and without 1,4-cyclohexanediol. The skin was separated into stratum corneum and the deeper skin layers. The azelaic acid collected in receptor medium and each layer at the end of each time point was extracted and quantified. A significant decrease in flux across the skin suggests a penetration retardation effect of 1,4-cyclohexanediol (42.50 μg/cm2/h in the presence of vs. 76.25 μg/cm2/h in the absence of) at active loading level of 1.13 mg/cm2. The penetration retardation effect was also observed at higher active loading level (2.82 mg/cm2). Furthermore, presence of 1,4-cyclohexanediol in the topical formulation did not reduce the skin and epidermal retention of azelaic acid, suggesting its potential use in the development of superior topical formation for reducing potential systematic side effect while maintaining therapeutic efficiency.