Nutrition Therapy by Nutrition Support Team: A Comparison of Multi-Chamber Bag and Customized Parenteral Nutrition in Hospitalized Patients.

This study aimed to investigate the activity of a nutrition support team (NST) and the trends of multi-chamber bag (MCB) and customized parenteral nutrition (PN) with NST consultations in South Korea. Data were obtained from the National Inpatient Sample Cohort between 2015 and 2020. Three datasets were constructed for NST consultation, MCB-PN product prescriptions, and aseptic preparation of total PN. The intersections of the NST consultation and each PN dataset were compiled into MCB-PN with NST or customized PN with a NST sub-dataset, respectively. Using personal identifiers, the patients' characteristics were evaluated in the NST cohort. A total of 91,384 reimbursements and 70,665 patients were included. The NST activity had increased by more than 50% over 6 years. Approximately 70% and 11%, respectively, of the NST cohort were classified into two subgroups: MCB-PN with NST (M-NST) and customized PN with NST (C-NST). M-NST had many elderly patients with cancer and showed a higher in-hospital mortality than C-NST (12.6% vs. 9.5%). C-NST included a larger number of patients under the age of 5 years, and the hospitalization period was more extended than M-NST (26.2 vs. 21.2 days). The present study showed that NST activities and the proportion of PN with NST consultation are gradually increasing in South Korea.

Amplified Fenton-Based Oxidative Stress Utilizing Ultraviolet Upconversion Luminescence-Fueled Nanoreactors for Apoptosis-Strengthened Ferroptosis Anticancer Therapy.

As an emerging anticancer strategy, ferroptosis has recently been developed in combination with current therapeutic modalities to overcome the existing limitations of conventional therapies. Herein, an ultraviolet (UV) upconversion luminescence-fueled nanoreactor is explored to combine ferroptosis and apoptosis through the UV-catalyzed Fenton reaction of an iron supplement (ferric ammonium citrate) loaded in a mesoporous silica layer in addition to the support of a chemotherapeutic agent (cisplatin) attached on the functionalized silica surface for the treatment of triple negative breast cancer (TNBC). The nanoplatform can circumvent the low penetration depth typical of UV light by upconverting near-infrared irradiation and emitting UV photons that convert Fe3+ to Fe2+ to boost the generation of hydroxyl radicals (·OH), causing devastating lipid peroxidation. Apart from DNA damage-induced apoptosis, cisplatin can also catalyze Fenton-based therapy by its abundant production of hydrogen peroxide (H2O2). As a bioinspired lipid membrane, the folate receptor-targeted liposome as the coating layer offers high biocompatibility and colloidal stability for the upconversion nanoparticles, in addition to prevention of the premature release of encapsulated hydrophilic compounds, before driving the nanoformulation to the target tumor site. As a result, superior antitumor efficacy has been observed in a 4T1 tumor-bearing mouse model with negligible side effects, suggesting that such a nanoformulation could play a pivotal role in effective apoptosis-strengthened ferroptosis TNBC therapy.

Combined phototherapy with metabolic reprogramming-targeted albumin nanoparticles for treating breast cancer.

Triple-negative breast cancer (TNBC) is characterized by rapid tumor growth and resistance to cancer therapy, and has a poor prognosis. Accumulating data have revealed that cancer metabolism relies on both the Warburg effect and oxidative phosphorylation (OXPHOS), which are strongly related to the high proliferation and chemoresistance of cancer cells. Phototherapy is considered as a non-invasive method to precisely control drug activity with reduced side effects. Herein, our group introduced an Abraxane-like nanoplatform, named LCIR NPs, which significantly eradicates cancer cells via synergism between metabolic reprogramming and phototherapy effects. Endowed with mitochondria-targeting residues, the nanoparticles efficiently inhibited mitochondrial complexes I and IV as well as hexokinase II, leading to the depletion of intracellular ATP. Consequently, the photodynamic and photothermal effect triggered by NIR irradiation was enhanced due to the alleviation of hypoxia and the thermoresistance mechanism that rely on mitochondrial metabolism. In vivo experiments showed that the tumor size of mice that received the combination treatment was only 50.7 mm3, which was 21 times smaller than that of the untreated group and was much lower than those of other single treatments after 21 days. Additionally, almost no systemic undesired toxicity was detected during the observation period. We believe that the concept of LCIR as presented here offers a potential platform to overcome the resistance to conventional therapies by the incorporation with the energy metabolism inhibition approach.

New potential application of hydroxypropyl-ß-cyclodextrin in solid self-nanoemulsifying drug delivery system and solid dispersion.

The purpose of this study was to use hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as a novel carrier in solid SNEDDS and solid dispersions to enhance the solubility and oral bioavailability of poorly water-soluble dexibuprofen. The novel dexibuprofen-loaded solid SNEDDS was composed of dexibuprofen, corn oil, polysorbate 80, Cremophor® EL, and HP-ß-CD at a weight ratio of 45/35/50/15/100. This solid SNEDDS spontaneously formed a nano-emulsion with a size of approximately 120 nm. Unlike the conventional solid SNEDDS prepared with colloidal silica as a carrier, this dexibuprofen-loaded solid SNEDDS exhibited a spherical structure. Similar to the dexibuprofen-loaded solid dispersion prepared with HP-ß-CD, the transformation of the crystalline drug to an amorphous state with no molecular interactions were observed in the solid SNEDDS. Compared to the solid dispersion and dexibuprofen powder, solid SNEDDS significantly enhanced drug solubility and AUC. Therefore, HP-ß-CD is a novel potential carrier in SNEDDS for improving the oral bioavailability of dexibuprofen.

Preparation and Characterization of a Lutein Solid Dispersion to Improve Its Solubility and Stability.

Lutein has been used as a dietary supplement for the treatment of eye diseases, especially age-related macular degeneration. For oral formulations, we investigated lutein stability in artificial set-ups mimicking different physiological conditions and found that lutein was degraded over time under acidic conditions. To enhance the stability of lutein upon oral intake, we developed enteric-coated lutein solid dispersions (SD) by applying a polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS-LF), through a solvent-controlled precipitation method. The SD were characterized in crystallinity, morphology, and drug entrapment. In the dissolution profile of lutein SD, a F80 formulation showed resistance toward the acidic environment under simulated gastric conditions while exhibiting a bursting drug release under simulated intestinal conditions. Our results highlight the potential use of HPMCAS-LF as an effective matrix to enhance lutein bioavailability during oral delivery and to provide novel insights into the eye-care supplement industry, with direct benefits for the health of patients.

Redox/photo dual-responsive, self-targeted, and photosensitizer-laden bismuth sulfide nanourchins for combination therapy in cancer.

Targeted and stimuli-sensitive nanobombs for the release of therapeutic agents after laser irradiation of the tumor site are gaining widespread attention as personalized anticancer regimens. In this study, redox and photo dual-responsive, folate receptor-targeted nanourchin carriers for chemo-, photodynamic, and photothermal therapy were constructed by the amalgamation of an outer layer of polyethylene glycol (PEG)-S-S-methotrexate (MTX) and an inner core of indocyanine green (ICG)-loaded bismuth sulfide (Bi2S3) nanoparticles for cancer treatment. MTX introduces the carrier to folate receptors resulting in the internalization of nanoparticles into cancer cells, specifically and increasingly. In the reducing environment inside cancer cells, MTX was cleaved, resulting in a burst release that effectively inhibited tumor growth. Simultaneously, the fusion of Bi2S3 and ICG in the inner core absorbed energy from a near-infrared radiation (NIR) laser to generate heat and reactive oxygen species, which further ablated the tumors and synergistically enhanced the anticancer activity of MTX. These results indicate the successful preparation of combined nanourchins (NUs) showing GSH-induced and laser-responsive release of MTX and ICG, accompanied by hyperthermia via Bi2S3 and ICG. Effective in vitro cellular internalization, cellular cytotoxicity, and pro-apoptotic behavior of the nanosystem were achieved through a targeting, redox, and NIR-responsive combination strategy. In vivo biodistribution and photothermal imaging also revealed tumor-selective and -retentive, as well as thermally responsive attributes. Ultimately, this in vivo antitumor study shows an effective tumor ablation by these nanourchins without affecting the vital organs. Our findings indicate that using these targeted redox- and laser-responsive combination therapeutic carriers can be a promising strategy in folate receptor-expressing tumors.

Indocyanine Green and Curcumin Co-Loaded Nano-Fireball-Like Albumin Nanoparticles Based on Near-Infrared-Induced Hyperthermia for Tumor Ablation.

BACKGROUND: Indocyanine green (ICG) has received considerable interest as a biocompatible organic photothermal agent, and curcumin (Cur) is considered an attractive natural chemopreventive and chemotherapeutic compound. However, the in vivo applicability of ICG and Cur is significantly restricted by their poor ability to target tumors and their extremely low solubility. MATERIALS AND METHODS: To address these problems, ICG/Cur-loaded albumin nanoparticles (ICG-BSA-Cur-NPs) based on the nabTM (nanoparticle albumin-bound) technology were applied to neuroblastomas in vivo. RESULTS: The fabricated ICG-BSA-Cur-NPs were found to be spherical, ~150 nm in size and highly dispersible and stable in aqueous solution. Approximately 80% of the incorporated ICG and Cur were gradually released from the NPs over 48 h. All formulations of ICG-BSA-Cur-NPs (5~20 µg/mL) showed efficient hyperthermia profiles (up to 50-60°C within 5 min) in response to 808-nm NIR laser irradiation in vitro and in vivo. Notably, ICG-BSA-Cur-NPs illuminated with 808-nm laser irradiation (1.5 W/cm2) showed excellent cytotoxicity toward N2a cells in vitro and undisputable antitumor efficacy in N2a-xenografted mice in vivo, compared to other tested sample groups (tumor volumes for PBS, BSA-Cur-NPs, free ICG, and ICG-BSA-Cur-NPs groups were 1408.6 ± 551.9, 1190.6 ± 343.6, 888.6 ± 566.2, and 103.0 ± 111.3 mm3, respectively). CONCLUSION: We demonstrate that these hyperthermal chemotherapeutic ICG-BSA-Cur-NPs have potential as a future brain tumor treatment.

Hyaluronic acid wreathed, trio-stimuli receptive and on-demand triggerable nanoconstruct for anchored combinatorial cancer therapy.

Hyaluronic acid (HA) assisted effective internalization into CD44 receptor-overexpressing cancer cells, which could offer an excellent cytotoxic profile and tumor alterations. In this study, duo-photothermal agents (copper sulfide (CuS) and graphene oxide (GO)), chemotherapeutic drug (doxorubicin (DOX)), and targeting moiety (HA) were incorporated into a complexed nanoconstruct for trio-responsive chemo-phototherapy. The nanosystem (CuS(DOX)-GO-HA) was demonstrating its responsive drug release and escalated photothermal behavior. The hyperthermia and photodynamic effect were observed along with efficient ROS generation in the presence of dual photosensitizers. The in vivo biodistribution and photothermal profile reflected a high accumulation and retention of the nanoconstruct in the tumor. Importantly, nanoconstructs effectively inhibit tumor growth based on tumor volume analysis and the altered expression of apoptosis, cell proliferation, and angiogenesis markers. Collectively, these findings suggest that this nanoconstruct has excellent antitumor effects in CD44 overexpressed cells showing the potential for clinical translation in the future.

Stealth Polymer-Coated Graphene Oxide Decorated Mesoporous Titania Nanoplatforms for In Vivo Chemo-Photodynamic Cancer Therapy.

PURPOSE: The goal of this study was to develop chemotherapeutic drug-loaded photoactivable stealth polymer-coated silica based- mesoporous titania nanoplatforms for enhanced antitumor activity. METHODS: Both in vitro and in vivo models of solvothermal treated photoactivable nanoplatforms were evaluated for efficient chemo-photothermal activity. A versatile nanocomposite that combined silica based- mesoporous titania nanocarriers (S-MTN) with the promising photoactivable agent, graphene oxide (G) modified with a stealth polymer (P) was fabricated to deliver chemotherapeutic agent, imatinib (I), (referred as S-MTN@IG-P) for near-infrared (NIR)-triggered drug delivery and enhanced chemo-photothermal therapy. RESULTS: The fabricated S-MTN@IG-P nanoplatform showed higher drug loading (~20%) and increased drug release (~60%) in response to light in acidic condition (pH 5.0). As prepared nanoplatform significantly converted NIR light into thermal energy (43.2°C) to produce reactive oxygen species (ROS). The pronounced cytotoxic effect was seen in both colon cancer cells (HCT-116 and HT-29) that was mediated through the chemotherapeutic effect of imatinib and the photothermal and ROS generation effects of graphene oxide. In vivo study also showed that S-MTN@IG-P could significantly accumulate into the tumor area and suppress the tumor growth under NIR irradiation without any biocompatibility issues. CONCLUSION: Cumulatively, the above results showed promising effects of S-MTN@IG-P for effective chemo-phototherapy of colon cancer.

Multi-responsive albumin-lonidamine conjugated hybridized gold nanoparticle as a combined photothermal-chemotherapy for synergistic tumor ablation.

Herein, we developed a multifunctional nanoplatform based on the nanoassembly of gold nanoparticles (GNP) conjugated with lonidamine (LND) and aptamer AS1411 (AS-LAGN) as an effective cancer treatment. Conjugating AS1411 aptamer on the surface of the nanoparticle significantly improved particle accumulation in cancer cells via specific affinity toward the nucleolin receptors. In vitro study clearly revealed that laser irradiation-based hyperthermia effect enhanced the chemotherapeutic effects of LND. Combinational treatment modalities revealed significant apoptosis with higher cell killing effect due to increased ROS production and inhibition of cell migration. GNP's ability to convert the excited state photon energy into thermal heat enabled synergistic photothermal/chemotherapy with improved therapeutic efficacy in animal models. Moreover, immunohistochemistry staining assays confirmed the ability of AS-LAGN to induce cellular apoptosis/necrosis and ablation in tumor tissues, without causing evident damages to the surrounding healthy tissues. Altogether, this AS-LAGN nanoplatform could be a promising strategy for mitochondria-based cancer treatment. STATEMENT OF SIGNIFICANCE: We have designed a facile biodegradable multifunctional nanocarrier system to target the mitochondria, the major "power house" of the cancer cells. We have constructed a multifunctional nanoassembly of protein coronated gold nanoparticles (GNP) conjugated with lonidamine (LND) and aptamer AS1411 (AS-LAGN) as an effective combination of phototherapy with chemotherapy for cancer treatment. The LND was conjugated with albumin which was in turn conjugated to GNP via redox-liable disulfide linkage to generate oxidative stress and ROS to kill cancer cells. GNP's ability to convert the excited state photon energy into thermal heat enabled synergistic photothermal/chemotherapy with improved therapeutic efficacy in animal models. Consistently, AS-LAGN showed enhanced antitumor efficacy in xenograft tumor model with remarkable tumor regression property.

Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate.

Purpose: The objective of this study was to exploit a novel methotrexate (MTX)-loaded solid self-microemulsifying drug delivery system (SMEDDS) with enhanced bioavailability and photostability. Materials and methods: The optimized liquid SMEDDS was composed of castor oil, Tween® 80, and Plurol® diisostearique at a voluminous ratio of 27:63:10. The solid SMEDDS was formulated by spray drying liquid SMEDDS with the solid carrier (calcium silicate). Particle size analyzer, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy experiments characterized the physiochemical properties of the MTX-loaded solid SMEDDS. These properties include a z-average diameter of emulsion around 127 nm and the amorphous form of the solid SMEDDS. Furthermore, their solubility, dissolution, and pharmacokinetics in Sprague-Dawley rats were analyzed in comparison with the MTX powder. Results: The final dissolution rate and required time for complete release of solid SMEDDS were 1.9-fold higher and 10 min shorter, respectively, than those of MTX powder. Pharmacokinetic analysis demonstrated 2.04- and 3.41-fold increments in AUC and Cmax, respectively in comparison to MTX powder. The AUC and Cmax were significantly increased in solid SMEDDS. Finally, the photostability studies revealed the substantially enhanced photostability of the MTX-loaded SMEDDS under the forced degradation and confirmatory conditions. Conclusion: This solid SMEDDS formulation could be an outstanding candidate for improving the oral bioavailability and photostability of MTX.

Multifaceted NIR-responsive polymer-peptide-enveloped drug-loaded copper sulfide nanoplatform for chemo-phototherapy against highly tumorigenic prostate cancer.

Targeted, biocompatible, and synergistic "all in one" systems should be designed to combat the heterogeneity of cancer. In this study, we constructed a dual function nanosystem, copper sulfide nanoplatform loaded with the chemotherapeutic drug docetaxel wrapped by a conjugated polymer-peptide for targeted chemo-phototherapy. The nanoconstruct has been successfully designed with a size of 186.1 ±â€¯5.2 nm, a polydispersity index of 0.18 ±â€¯0.01, and zeta potential of -16.4 ±â€¯0.1 mV. The enhanced uptake and near-infrared-responsive behavior of the nanosystem resulted in efficient drug release, photothermal ablation, effective cytotoxic activity, and potentiated reactive oxygen species generation. The induction of apoptotic markers, enhanced accumulation in the tumor site, and maximum tumor growth inhibition were seen during in vivo studies compared to non-targeted nanoformulations and free drug. Cumulatively, our results indicate that, with low systemic toxicity and better biocompatibility, this nanoconstruct could provide a promising strategy for treating prostate cancer.

Gold nanocluster-loaded hybrid albumin nanoparticles with fluorescence-based optical visualization and photothermal conversion for tumor detection/ablation.

Gold nanoclusters (AuNCs) are viewed as effective hyperthermal agents for the treatment of tumors. Whereas AuNCs formed by the agglomeration of several to tens of gold atoms (<1-2 nm) possess significant fluorescence, they have a negligible hyperthermal effect, while AuNCs comprised of spherical gold nanoparticles (AuNPs > a few nanometers) have a marked hyperthermic effect but lose their inherent fluorescence and obstruct the intensity of neighboring fluorescent dyes due to Forster resonance energy transfer (FRET). To achieve both hyperthermia and fluorescence-based optical visualization, we generated hybrid albumin nanoparticles containing AuNCs (~88 nm) comprising AuNPs (~4.5 nm). We generated a series of formulated AuNCs and optimized the size, morphology, NIR absorbance (600-900 nm), hyperthermal activity, and fluorescence spectral characters of the resulting hybrid albumin nanoparticles (AuNCs/BSA-NPs) by considering the interparticle distance between the AuNPs and Cy5.5. Among these, AuNCs/BSA-NPs (formula D) had a strong hyperthermic effect and had well-preserved fluorescence intensity (from the attached Cy5.5) due to localized surface plasmon resonance (LSPR) and a reduction in FRET. These AuNCs/BSA-NPs were able to elevate the surface tumor temperature of HCT116-bearing mice to >50 °C following 808 nm laser irradiation (1.5 W/cm2, 10 min), which remarkably suppressed tumor growth (17.8 ±â€¯16.9 mm3vs. PBS and AuNCs/BSA-NPs (formula E): ~1850 and ~1250 mm3, respectively). Also, Cy5.5-modified AuNCs/BSA-NPs (formula D) showed good performance in optical fluorescence imaging of target tumors in HCT116 tumor-bearing mice. Together, our results indicate that the interparticle distance between albumin or Cy5.5 and AuNPs/AuNCs can be optimized to achieve both hyperthermia and fluorescence emission by striking a balance between LSPR and FRET effects. We believe that the AuNC/BSA-NPs formulation presented here can serve as a potential platform for both optically visualizing and treating colon cancers.

Small gold nanorods-loaded hybrid albumin nanoparticles with high photothermal efficacy for tumor ablation.

Photothermal therapy using gold nanorods (AuNRs) has gained great attention for cancer therapy because AuNRs emit heat and induce tumor cell death responding to the near infrared light. However, the anticancer efficiency of AuNRs alone is undermined by its poor in vivo stability and potential toxicity. The prime purpose of this study was to send more AuNRs into tumors to more fully ablate them. For this, we fabricated hybrid albumin nanoparticles encapsulating small AuNRs (AuNRs-Alb-NPs), which take advantage of biocompatible albumin as a carrier, with better tumor targetability and high in vivo photothermal activity. The sizes of length/width of AuNRs were approximately 20.5 nm and 4.6 nm, respectively, showing a 4.5 aspect ratio, and the size of the resulting AuNRs-Alb-NPs was ˜130 nm, all of which are favorable for glomerular filtration and passive tumor targeting via extravasation. We chose the best formulation for AuNRs-Alb-NPs by in vitro cytotoxicity based on photothermal conversion efficiency considering the incorporated number of AuNRs. Visualized by a photothermal camera, the local tumor temperature of mice treated with AuNRs-Alb-NPs increased to 57℃, which was sufficient for the hyperthermal effect with 808 nm laser irradiation. Subsequently, AuNRs-Alb-NPs displayed remarkably better tumor ablation vs. naïve formulation of AuNRs (tumor volume: 73.8 ± 105.8 vs. 1455.3 ± 310.4 mm3 at day 8) in the glioblastoma N2a tumor-bearing mice. Most of all, we demonstrated, using photoacoustic imaging and inductively coupled plasma mass spectrometry, that this much better tumor ablation was due to enhanced tumor targeting with albumin nanoparticles. We believe our AuNRs-Alb-NPs should be considered promising photothermal agents that are safer, have good targetability, and exhibit excellent tumor ablation.

Aerosol technique-based carbon-encapsulated hollow mesoporous silica nanoparticles for synergistic chemo-photothermal therapy.

Near-infrared (NIR)-responsive drug delivery systems have enhanced tumor ablative efficiency through permeation and retention effects. Graphene oxide (GO) has shown great potential both in photothermal therapy and in drug delivery. Thus, in this study, we designed an ambient spark-generated GO, wrapped on topotecan (TPT)-loaded hollow mesoporous silica nanoparticles (HMSN-NH2-TPT-CGO), to function as an efficient platform for pH-dependent sustained release of TPT. HMSN-NH2-TPT-CGO also exhibited a combined chemo-photothermal effect within a single carrier system. This developed system was stable with a uniform particle size (∼190 nm) and was demonstrated to possess a sufficient heat-absorbing capacity to induce tumor cell ablation. We performed the ablation of tumor cells both in vitro and in vivo in combination with photothermal therapy and chemotherapy using the spark-generated functional GO and HMSN. The prepared nanocarriers demonstrated high cellular uptake, apoptosis, and G0/G1 cell cycle arrest. In vivo study using the MDA-MB-231 xenograft model revealed the ultraefficient tumor ablative performance of HMSN-NH2-TPT-CGO compared with that of free TPT, with no toxic effect on vital organs. Altogether, the optimized nanocarriers presented a significant potential to act as a vehicle for cancer treatment. STATEMENT OF SIGNIFICANCE: This is the first study that uses spark-generated graphene oxide nanoflakes to cover the topotecan (TPT)-loaded hollow mesoporous silica nanoparticles (HMSNs) to treat breast cancer. Dense silica was used as a hard template to prepare the HMSNs attributing to a high drug payload. The concentration of Na2CO3 was precisely controlled to minimize the silica etching time within 70 min. The use of the nanographene flakes served a dual purpose, first, by acting as a capping agent to prevent the premature release of drug and, second, by serving as a nano heater that significantly ablates the tumor cells. The prepared nanocarriers (NCs) exhibited effective and enhanced in vitro and in vivo apoptosis, as well as significant tumor growth inhibition even after 15 days of treatment time, with no toxic effect to the vital organs. The NCs enhanced in vitro tumor cell killing effects and served as an effective carrier for in vivo tumor regression, thereby highlighting the enormous potential of this system for breast cancer therapy.

Copper sulfide: An emerging adaptable nanoplatform in cancer theranostics.

Copper sulfide nanoparticles (CuS NPs), emerging nanoplatforms with dual diagnostic and therapeutic applications, are being actively investigated in this era of "war on cancer" owing to their versatility and adaptability. This article discusses the pros and cons of using CuS NPs in diagnostics, therapeutics, and theranostics. The first section introduces CuS NPs and discusses the features that render them more advantageous than other established nanoplatforms in cancer management. Subsequent sections include specific in vitro and in vivo results of different studies showing the potential of CuS NPs as nanoplatforms. Methods used for visualization (photoacoustic imaging and magnetic resonance imaging) of CuS NPs and treatment (phototherapy and combinatorial therapy) have also been discussed. Furthermore, the challenges and opportunities associated with using CuS NPs have been elucidated. Further investigations on CuS NPs are required to translate it for clinical applications.

Transferrin-conjugated pH-sensitive platform for effective delivery of porous palladium nanoparticles and paclitaxel in cancer treatment.

Porous palladium (Pd) nanoparticles have garnered great research attention due to their potential anticancer activity and photothermal effect. In this study, a transferrin-conjugated pH-sensitive platform (Tf-PPP), comprising porous Pd nanoparticles (PdNPs) and paclitaxel (PTX), was successfully developed for combined chemo-phototherapy. Tf-PPPs have a small size of 164.6 ± 8.7 nm, PDI of 0.278 ± 0.029, and negative charge (-13.2 ± 1.8 mV). Poly(acrylic acid)-poly(ethylene oxide) (PAA-PEO), a pH sensitive polymer, was used to achieve pH-dependent drug release from nanoparticles. Transferrin (Tf) conjugated on the surface of nanoplatforms could enhance the cellular uptake and prolong nanoparticle accumulation in the tumor site. The combination of phototherapy induced by PdNPs and chemotherapeutic agent (PTX) could exhibit synergistic anticancer activities. Consistent findings were observed in both in vitro experiments including cytotoxicity, live/dead assay, and assessment of apoptotic protein levels, and in vivo antitumor study in MCF-7 tumor-bearing mice, with results decreasing in the following order: Tf-PPPs + NIR > Tf-PPPs > PPPs + NIR > PPPs > PTX > PdNPs. These findings suggest that the administration of Tf-PPPs, followed by NIR irradiation could be a promising strategy in the treatment of cancer.

Near infrared light-responsive heat-emitting hemoglobin hydrogels for photothermal cancer therapy.

Photothermal therapy (PTT) is an effective means of treating tumors because tumor cells are sensitive to heat. Gold and carbon nanoparticles are used as efficient PTT materials. However, development of a non-toxic biodegradable PTT agent remains a challenge. Here, we developed a hemoglobin (Hb) hydrogel that exhibited excellent PTT effects in vitro and in vivo. Unlike conventional PTT agents, which are toxic and do not decompose completely in the body, the Hb hydrogel was manufactured using only two components: (i) Hb, a natural substance derived from the human body, and (ii) PEG, an FDA-approved polymer. The gelation time of the Hb hydrogels could be controlled by changing the Hb concentration. Because Hb is present at a high concentration (150 mg/ml) in the body, the Hb hydrogel decomposed and was eliminated in vivo without toxicity. The Hb hydrogel showed an excellent PTT effect in response to 808 nm near-infrared (NIR) laser irradiation and had excellent anticancer effects against A549 lung cancer cells both in vitro and in vivo. Blood hematology and blood biochemical assay results from an animal model treated with Hb hydrogel were similar to those of the control group. Importantly, toxicity was not observed based on H&E staining of major organs (heart, liver, spleen, kidneys and lung). Tumors of A549 cell-xenografted mice treated with Hb hydrogel and 808 nm NIR laser irradiation were significantly smaller than those of the control group (23.1 mm3versus 746.5 mm3, respectively). This is a first report of a biocompatible photothermal hydrogel based on hemoglobin, and our overall results suggest that Hb hydrogels are commercially-promising PTT systems that have excellent anti-cancer effects.

Facile fabrication of highly photothermal-effective albumin-assisted gold nanoclusters for treating breast cancer.

Gold nanoclusters (AuNCs) have been considered to be a promising candidate for hyperthermia-based anticancer therapy. Herein, we introduce albumin-assisted AuNCs composed of small gold nanoparticles (AuNPs, <6 nm) assembled with strands of polyallylamine (PAH), which exhibited strong surface plasmon resonance upon near-infrared (NIR, ∼808 nm) laser irradiation and good in vivo stability. Our albumin-assisted PAH-AuNCs (BSA/PAH-AuNCs) were facilely fabricated as a top-down process by a simple ultrasonication after the preparation of large nano-aggregates of PAH-AuNPs. Albumin played a critical role as a stabilizer and surfactant in making loosely associated large aggregates and thereby producing small gold nanoclusters (∼60 nm) of slightly negative charge upon ultrasonication. The prepared BSA/PAH-AuNCs displayed excellent hyperthermal effects (∼60 °C) in response to ∼808-nm NIR laser irradiation in a 4T1 cell system in vitro and in 4T1 cell tumor xenograft mice in vivo, indicating their remarkable potential to suppress breast cancer growth, without almost no significant toxicity in histology. Consequently, our gold nanoclusters should be considered as a promising photothermal agent that are easy to manufacture and exhibit marked anticancer effects in terms of tumor ablation.

Combination of NIR therapy and regulatory T cell modulation using layer-by-layer hybrid nanoparticles for effective cancer photoimmunotherapy.

The efficacy of combined near-infrared (NIR) and immune therapies for inhibiting tumor growth and recurrence has gained increasing research attention. Regulatory T cells in the tumor microenvironment constitute a major obstacle in achieving robust CD8+ T cell antitumor immunotherapy. In the present study, we designed a photoimmunotherapy-based strategy involving a combination of photothermal and photodynamic therapies, followed by Treg cell suppression, for eliciting an immune response with IR-780- and imatinib-loaded layer-by-layer hybrid nanoparticles. Methods: The layer-by-layer hybrid nanoparticles were prepared through electrostatic interactions. Their photothermal effect, photodynamic effect as well as their effect on inhibiting Treg cells' suppressive function were investigated in vitro and in vivo. Their antitumor effect was evaluated using B16/BL6 and MC-38 tumor-bearing mice. Results: The layer-by-layer hybrid nanoparticles, which were pH-sensitive, enabled the release of IR-780 dye for NIR-induced photothermal and photodynamic effects, and the release of imatinib-loaded glucocorticoid-induced TNF receptor family-related protein/poly(lactic-co-glycolic acid) (GITR-PLGA) nanoparticles to initiate antitumor immunotherapy. The photothermal and photodynamic effects caused by IR-780 under NIR exposure resulted in direct tumor apoptosis/necrosis and the production of tumor-associated antigen, promoted dendritic cell maturation, and enhanced the presentation of tumor-associated antigen to T cells, while the imatinib-loaded GITR-PLGA cores reduced the suppressive function of Treg cells, and consequently activated effective CD8+ T cells towards tumors. Conclusion: With the significant photothermal, photodynamic and immunotherapies, the system successfully eradicated tumor growth, diminished tumor recurrence, and improved survival in vivo. The proposed nanoparticles provide a novel and versatile approach to boost antitumor photoimmunotherapy.