A Pd corolla-human serum albumin-indocyanine green nanocomposite for photothermal/photodynamic combination therapy of cancer.

In this work, a novel nanoplatform based on Pd corolla-human serum albumin-indocyanine green (PdCs-HSA-ICG) was developed for cancer photothermal/photodynamic combination therapy. Pd corollas (denoted as PdCs) with good near-infrared photothermal conversion efficiency (η≈ 37%) were first prepared and modified with human serum albumin (HSA) and indocyanine green (ICG) to get the PdCs-HSA-ICG nanocomposite. The prepared PdCs-HSA-ICG not only improves the colloid and thermal stability of ICG, but also shows a higher temperature increase than that of PdCs and free ICG as well as a comparable singlet oxygen (1O2) generation capability to that of free ICG. Upon single 808 nm laser irradiation, the photothermal (PTT)/photodynamic (PDT) combined therapeutic efficacy of PdCs-HSA-ICG at both cellular and animal levels was superior to PdCs-HSA (PTT) or free ICG (PTT and PDT), respectively. Thus, the designed PdCs-HSA-ICG nanocomposite holds great potential as a new class of photosensitive agent for cancer phototherapy.

Platinum(IV) prodrug conjugated Pd@Au nanoplates for chemotherapy and photothermal therapy.

Owing to the excellent near infrared (NIR) light absorption and efficient passive targeting toward tumor tissue, two-dimensional (2D) core-shell PEGylated Pd@Au nanoplates have great potential in both photothermal therapy and drug delivery systems. In this work, we successfully conjugate Pd@Au nanoplates with a platinum(IV) prodrug c,c,t-[Pt(NH3)2Cl2(O2CCH2CH2CO2H)2] to obtain a nanocomposite (Pd@Au-PEG-Pt) for combined photothermal-chemotherapy. The prepared Pd@Au-PEG-Pt nanocomposite showed excellent stability in physiological solutions and efficient Pt(IV) prodrug loading. Once injected into biological tissue, the Pt(IV) prodrug was easily reduced by physiological reductants (e.g. ascorbic acid or glutathione) into its cytotoxic and hydrophilic Pt(II) form and released from the original nanocomposite, and the NIR laser irradiation could accelerate the release of Pt(II) species. More importantly, Pd@Au-PEG-Pt has high tumor accumulation (29%ID per g), which makes excellent therapeutic efficiency at relatively low power density possible. The in vivo results suggested that, compared with single therapy the combined thermo-chemotherapy treatment with Pd@Au-PEG-Pt resulted in complete destruction of the tumor tissue without recurrence, while chemotherapy using Pd@Au-PEG-Pt without irradiation or photothermal treatment using Pd@Au-PEG alone did not. Our work highlights the prospects of a feasible drug delivery strategy of the Pt prodrug by using 2D Pd@Au nanoplates as drug delivery carriers for multimode cancer treatment.

Simultaneous Enhancement of Intracellular Optical Imaging and Photothermal Therapeutic Response by Octaarginine-Modified Fluorescent Dye Doped Pd@Ag@SiO2(RITC) Multifunctional Nanoparticles.

In the work, a novel multifunctional silica-based nanoplatform (Pd@Ag@SiO2(RITC)-R8) for bioimaging and photothermal therapy (PTT) of cancer cells has been developed. The Pd@Ag nanosheets encapsulated inside silica can act as effective near-infrared (NIR) absorbers for cancer photothermal therapy. Fluorescent dye, rhodamine B isothiocyanate (RITC), was covalently doped into the silica network to provide the capacity for optical imaging. After amine modification, the Pd@Ag@SiO2(RITC)-NH2 can be further conjugated with octaarginine (R8, a cell penetrating peptide) for enhancing the uptake of nanoparticles by cells. Confocal fluorescent images and flow cytometry analysis revealed that R8-conjugated nanoparticles (Pd@Ag@SiO2(RITC)-R8) were taken up by cells more efficiently. Correspondingly, the optical imaging and photothermal therapeutic efficiency of Pd@Ag@SiO2(RITC)-R8 upon cancer cells were also raised due to their higher cellular uptake when compared with that of Pd@Ag@SiO2(RITC)-NH2. Our results indicate that these multifunctional Pd@Ag@SiO2(RITC)-R8 may have great potential for applications in imaging-guided cancer photothermal therapy.

Optimization of Surface Coating on Small Pd Nanosheets for in Vivo near-Infrared Photothermal Therapy of Tumor.

Palladium nanosheets with strong near-infrared absorption have been recently demonstrated as promising photothermal agents for photothermal therapy (PTT) of cancers. However, systematic assessments of their potential risks and impacts to biological systems have not been fully explored yet. In this work, we carefully investigate how surface coatings affect the in vivo behaviors of small Pd nanosheets (Pd NSs). Several biocompatible molecules such as carboxymethyl chitosan (CMC), PEG-NH2, PEG-SH, and dihydrolipoic acid-zwitterion (DHLA-ZW) were used to coat Pd NSs. The blood circulation half-lives, biodistribution, potential toxicity, clearance, and photothermal effect of different surface-coated Pd NSs in mice after intravenous injection were compared. PEG-SH-coated Pd NSs (Pd-HS-PEG) were found to have ultralong blood circulation half-life and show high uptake in the tumor. We then carry out the in vivo photothermal therapeutic studies on the Pd-HS-PEG conjugate and revealed its outstanding efficacy in in vivo photothermal therapy of cancers. Our results highlight the importance of surface coatings to the in vivo behaviors of nanomaterials and can provide guidelines to the future design of Pd NSs bioconjugates for other in vivo applications.

Copper sulfide nanoparticles with phospholipid-PEG coating for in vivo near-infrared photothermal cancer therapy.

In this work, small sizes of hydrophobic copper sulfide nanoparticles (CuS NPs, ∼3.8 nm in diameter) have been successfully prepared from the reaction of copper chloride with sodium diethyldithiocarbamate (SDEDTC) inside a heated oleylamine solution. These CuS NPs displayed strong absorption in the 700-1100 nm near-infrared (NIR) region. By coating CuS NPs with DSPE-PEG2000 on the surface, the as-synthesized CuS@DSPE-PEG NPs exhibited good water solubility, significant stability and biocompatibility, as well as excellent photothermal conversion effects upon exposure to an 808 nm laser. After intravenous administration to mice, the CuS@DSPE-PEG NPs were found to passively target to the tumor site, and tumor tissues could be ablated efficiency under laser irradiation. In addition, CuS@DSPE-PEG NPs do not show significant toxicity by histological and blood chemistry analysis, and can be effectively excreted via metabolism. Our results indicated that CuS@DSPE-PEG NPs can act as an ideal photothermal agent for cancer photothermal therapy.

Simultaneous photodynamic and photothermal therapy using photosensitizer-functionalized Pd nanosheets by single continuous wave laser.

In this work, we prepared chlorin e6 (Ce6)-functionalized Pd nanosheets (Pd-PEI-Ce6) for the photodynamic and photothermal combined therapy that use a single laser. To fabricate the Pd-PEI-Ce6 nanocomposite, photosensitizer Ce6 were chemically conjugated to polyethylenimine (PEI) and the formed Ce6-PEI conjugates were then anchored onto Pd nanosheets by electrostatic and coordination interaction. The prepared Pd-PEI-Ce6 nanocomposite were about 4.5 nm in size, exhibited broad, and strong absorption from 450 to 800 nm, good singlet oxygen generation capacity and photothermal conversion efficiency, and excellent biocompability. Significantly greater cell killing was observed when HeLa cells incubated with Pd-PEI-Ce6 were irradiated with the 660 nm laser, attributable to both Pd nanosheets-mediated photothermal ablation and the photodynamic destruction effect of photosensitizer Ce6. The double phototherapy effect was also confirmed in vivo. It was found that the Pd-PEI-Ce6 treated tumor-bearing mice displayed the enhanced therapeutic efficiency compared to that of Pd-PEI, or Ce6-treated mice. Our work highlights the promise of using Pd nanosheets for potential multimode cancer therapies.

Photothermally enhanced photodynamic therapy based on mesoporous Pd@Ag@mSiO2 nanocarriers.

In this work, we have demonstrated that mesoporous silica-coated Pd@Ag nanoparticles (Pd@Ag@mSiO2) can be used as an excellent nanoplatform for photodynamic therapy (PDT) drug delivery. Photosensitizer molecules, Chlorin e6 (Ce6), are covalently linked to the mesoporous shell and the prepared Pd@Ag@mSiO2-Ce6 nanoparticles exhibit excellent water solubility, good stability against leaching and high efficiency in photo-generating cytotoxic singlet oxygen. More importantly, the photothermal effect of Pd@Ag nanoplates under the irradiation of a NIR laser can enhance the uptake of Pd@Ag@mSiO2-Ce6 nanoparticles by cells, further increasing the PDT efficiency toward cancer cells. The photothermally enhanced PDT effects were demonstrated both in vitro and in vivo. When the Pd@Ag@mSiO2-Ce6 nanoparticles were injected intratumorally into the S180 tumor-bearing mice, the tumors were completely destroyed without recurrence of tumors upon irradiation with both 808 nm and 660 nm lasers, while the irradiation with 808 nm or 660 nm alone did not. These results indicate that the Pd@Ag@mSiO2 nanoparticles may be a valuable new tool for application in cancer phototherapy.