Mesenchymal stem cell-derived extracellular vesicles for treatment of bone loss within periodontitis in pre-clinical animal models: a meta-analysis.

BACKGROUND: Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) represent an effective and promising strategy for periodontitis, although studies remain pre-clinical. Herein, a meta-analysis was conducted to assess the efficacy of MSC-EVs in animal models of periodontitis. METHODS: The PubMed, Web of Science, and Embase electronic databases were searched up to Dec 2022 to retrieve preclinical studies examining the use of MSC-EVs for periodontitis treatment. Meta-analyses and sub-group analyses were performed to assess the effect of MSC-EVs on Bone Volume/Total Volume (BV/TV) or the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) in pre-clinical animal models of periodontitis. RESULTS: 11 studies published from Mar 2019 to Oct 2022 met the inclusion criteria. Overall, MSC-EVs contributed to periodontal bone regeneration in the inflammatory bone loss area due to periodontitis, as represented by a weighted mean difference (WMD) of 14.07% (95% CI = 6.73, 21.41%, p < 0.001) for BV/TV and a WMD of -0.12 mm (95% CI= -0.14, -0.11 mm, p < 0.001) for CEJ-ABC. However, sub-analysis suggested that there was no significant difference in CEJ-ABC between studies with bioactive scaffolds and studies without bioactive scaffolds (p = 0.60). CONCLUSIONS: The present study suggests that MSC-EVs may represent an attractive therapy for the treatment of inflammatory bone loss within periodontitis.

Dual Cross-linked HHA Hydrogel Supplies and Regulates MΦ2 for Synergistic Improvement of Immunocompromise and Impaired Angiogenesis to Enhance Diabetic Chronic Wound Healing.

Immunocompromise and impaired angiogenesis of diabetes lead to chronic inflammation when wounds occur, which is the primary reason for the long-term incurable nature of diabetic chronic wounds. Herein, a high-molecular-weight hyaluronic acid (HHA) hydrogel is developed to supply and regulate M2 phenotype macrophages (MΦ2) for synergistic improvement of immunocompromise and impaired angiogenesis. MΦ2 are seeded on the Cu-HHA/PVA hydrogels prepared by Cu2+ cross-linking of low degree and physical cross-linking (one freeze-thaw cycle and unique lyophilization) to form Cu-HHA/PVA@MΦ2 hydrogels. The Cu-HHA/PVA@MΦ2 hydrogel can directly supply the MΦ2 in the wound site, maintain the consistent phenotype of loaded MΦ2, and transform the M1 phenotype macrophages (MΦ1) in the wound bed to MΦ2 by HHA. Furthermore, Cu2+ could be released from the hydrogels to further stimulate angiogenesis, thus accelerating the wound-healing phase transition from inflammation to proliferation and remodeling. The average wound area after the 0.5Cu-HHA/PVA@MΦ2 (ionic cross-linking degree 0.5%) treatment was much smaller than that of other diabetic groups at day 12 and close to that of the wild nondiabetic control group. Therefore, this facile hydrogel strategy with multiple modulation mechanisms of immunocompromise and angiogenesis may act as a safe and effective treatment strategy for a diabetic chronic wound.

Amino-Modified Polymer Nanoparticles as Adjuvants to Activate the Complement System and to Improve Vaccine Efficacy in Vivo.

Subunit vaccines are safer but often poorly immunogenic in comparison to traditional vaccines, and thus, adjuvants and delivery vehicles are needed to enhance the immune response. The complement system is a part of the innate immune system, which plays an important role in innate and adaptive immunity. Therefore, the activation of the complement system could be utilized as a potential strategy for vaccine applications. Herein, cysteamine hydrochloride was grafted onto a methoxy poly(ethylene glycol)-block-poly (allyl glycidyl ether)-block-poly(ε-caprolactone) copolymer to synthesize a triblock polymer mPEG5k-PAGE15(NH2)-PCL5k(TPCAH) with amino groups on the side chain. The positive charge of the amino groups could bind with the negatively charged protein (like ovalbumin (OVA)) to form a stable complex by electrostatic interaction. The triblock copolymer TPCAH we designed can easily self-assemble into polymer nanomicelles, and the size of the nanoparticles is similar to that of the pathogens, which was beneficial to the uptake by lymphocytes. Furthermore, the amino groups modified on the side chain can not only integrate with proteins but also activate the complement system, thereby enhancing the immune response of subunit vaccines. The results showed that the complex TPCAH@OVA could efficiently promote powerful anti-OVA-specific antibody production, enhance CD4+ T- and CD8+ T-cell activation, improve the lymphocyte proliferation efficiency, and increase the secretion of different cytokines. In addition, the abundant amino groups on the surface of TPCAH@OVA could effectively activate the complement system to further enhance adaptive immunity. Overall, these results indicated that the triblock copolymer TPCAH as an adjuvant and carrier can effectively improve the ability of innate and adaptive immune responses to resist pathogens, making it a potential candidate for vaccine applications.

Amphiphilic Polycarbonates from Carborane-Installed Cyclic Carbonates as Potential Agents for Boron Neutron Capture Therapy.

Carboranes with rich boron content have showed significant applications in the field of boron neutron capture therapy. Biodegradable derivatives of carborane-conjugated polymers with well-defined structure and tunable loading of boron atoms are far less explored. Herein, a new family of amphiphilic carborane-conjugated polycarbonates was synthesized by ring-opening polymerization of a carborane-installed cyclic carbonate monomer. Catalyzed by TBD from a poly(ethylene glycol) macroinitiator, the polymerization proceeded to relatively high conversions (>65%), with low polydispersity in a certain range of molecular weight. The boron content was readily tuned by the feed ratio of the monomer and initiator. The resultant amphiphilic polycarbonates self-assembled in water into spherical nanoparticles of different sizes depending on the hydrophilic-to-hydrophobic ratio. It was demonstrated that larger nanoparticles (PN150) were more easily subjected to protein adsorption and captured by the liver, and smaller nanoparticles (PN50) were more likely to enter cancer cells and accumulate at the tumor site. PN50 with thermal neutron irradiation exhibited the highest therapeutic efficacy in vivo. The new synthetic method utilizing amphiphilic biodegradable boron-enriched polymers is useful for developing more-selective and -effective boron delivery systems for BNCT.

Single-Stimulus Dual-Drug Sensitive Nanoplatform for Enhanced Photoactivated Therapy.

Photoactivated therapy has become a complementary and attractive modality for traditional cancer treatment. Herein, we demonstrated a novel single-stimulus dual-drug sensitive nanoplatform, Cur-loaded Dex-Pt(N3) nanoparticles (Cur@DPNs) for enhanced photoactivated therapy. The developed Cur@DPNs could be photoactivated by UVA light to simultaneously generate instant reactive oxygen species from Cur for fast photodynamic therapy and release lasting Pt(II) from Pt(N3) for long-acting photochemotherapy. Compared with small free drugs and individual photoactivated therapy, Cur@DPNs exhibited enhanced photoactivated cytotoxicity and in vivo antitumor efficacy with low systemic toxicity accompanied. Therefore, the single-stimulus dual-drug sensitive nanoplatform is convinced to be a promising strategy for multidrug delivery, site-selective and combinational photoactivated therapy in the near future.

Doxorubicin-Loaded Carborane-Conjugated Polymeric Nanoparticles as Delivery System for Combination Cancer Therapy.

Carborane-conjugated amphiphilic copolymer nanoparticles were designed to deliver anticancer drugs for the combination of chemotherapy and boron neutron capture therapy (BNCT). Poly(ethylene glycol)-b-poly(L-lactide-co-2-methyl-2(2-dicarba-closo-dodecarborane)propyloxycarbonyl-propyne carbonate) (PLMB) was synthesized via the versatile reaction between decaborane and side alkynyl groups, and self-assembled with doxorubicin (DOX) to form drug-loaded nanoparticles. These DOX@PLMB nanoparticles could not only suppress the leakage of the boron compounds into the bloodstream due to the covalent bonds between carborane and polymer main chains, but also protect DOX from initial burst release at physiological conditions because of the dihydrogen bonds between DOX and carborane. It was demonstrated that DOX@PLMB nanoparticles could selectively deliver boron atoms and DOX to the tumor site simultaneously in vivo. Under the combination of chemotherapy and BNCT, the highest tumor suppression efficiency without reduction of body weight was achieved. This polymeric nanoparticles delivery system could be very useful in future chemoradiotherapy to obtain improved therapeutic effect with reduced systemic toxicity.

Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus.

Clinical studies have demonstrated that conditionally replicating adenovirus is safe. We constructed an oncolytic adenovirus, Ad-hTERT-E1a-Apoptin, using a cancer-specific promoter (human telomerase reverse transcriptase promoter, hTERTp) and a cancer cell-selective apoptosis-inducing gene (Apoptin). Ad-hTERT-E1a-Apoptin was proven effective both in vitro and in vivo in our previous study. In this study, the preclinical safety profiles of Ad-hTERT-E1a-Apoptin in animal models were investigated. At doses of 5.0×10(8), 2.5×10(9), and 1.25×10(10) viral particles (VP)/kg, Ad-hTERT-E1a-Apoptin had no adverse effects on mouse behavior, muscle cooperation, sedative effect, digestive system, and nervous systems, or on beagle cardiovascular and respiratory systems at 5.0×10(8), 2.5×10(9), and 1.25×10(10) VP/kg doses. In acute toxicity tests in mice, the maximum tolerated dose>5×10(10) VP/kg. There was no inflammation or ulceration at the injection sites within two weeks. In repeat-dose toxicological studies, the no observable adverse effect levels of Ad-hTERT-E1a-Apoptin in rats (1.25×10(10) VP/kg) and beagles (2.5×10(9) VP/kg) were 62.5- and 12.5-fold of the proposed clinical dose, respectively. The anti-virus antibody was produced in animal sera. Bone marrow examination revealed no histopathological changes. Guinea pigs sensitized by three repeated intraperitoneal injections of 1.35×10(10) VP/mL Ad-hTERT-E1a-Apoptin each and challenged by one intravenous injection of 1.67×10(8) VP/kg Ad-hTERT-E1a-Apoptin did not exhibit any sign of systemic anaphylaxis. Our data from different animal models suggest that Ad-hTERT-E1a-Apoptin is a safe anti-tumor therapeutic agent.

Generation of an attenuated Tiantan vaccinia virus by deletion of the ribonucleotide reductase large subunit.

Attenuation of the virulence of vaccinia Tiantan virus (VTT) underlies the strategy adopted for mass vaccination campaigns. This strategy provides advantages of safety and efficacy over traditional vaccines and is aimed at minimization of adverse health effects. In this study, a mutant form of the virus, MVTT was derived from VTT by deletion of the ribonucleotide reductase large subunit (R1) (TI4L). Compared to wild-type parental (VTT) and revertant (VTT-rev) viruses, virulence of the mutant MVTT was reduced by 100-fold based on body weight reduction and by 3,200-fold based on determination of the intracranial 50% lethal infectious dose. However, the immunogenicity of MVTT was equivalent to that of the parental VTT. We also demonstrated that the TI4L gene is not required for efficient replication. These data support the conclusion that MVTT can be used as a replicating virus vector or as a platform for the development of vaccines against infectious diseases and for cancer therapy.

The efficacy and safety of corticotomy and periodontally accelerated osteogenic orthodontic interventions in tooth movement: an updated meta-analysis.

BACKGROUND: The surgically facilitated orthodontic strategy has been a promising strategy for orthodontic treatment recently. Therefore, the present meta-analysis was conducted to assess the available scientific evidence regarding the clinical outcomes, including the potential detrimental effects associated with these surgical procedures, with the aim of providing much more evidence-based information for clinical practice. METHODS: An electronic search of three databases (PubMed, Cochrane, and Embase) and a manual search of relevant articles published up to May 2023 were carried out. Clinical trials (≥ 10 subjects) that utilized surgically facilitated orthodontic strategies with clinical and/or radiographic outcomes were included. Meta-analyses and sub-group analyses were performed to analyze the standardized mean difference (SMD) or weighted mean difference (WMD), and confidence interval (CI) for the recorded variables. RESULTS: Nineteen studies published from Oct 2012 to May 2023 met the inclusion criteria. Based on the analysis outcomes, corticotomy treatment significantly decreased the alignment duration (WMD: -1.08 months; 95% CI = -1.65, -0.51 months, P = 0.0002), and accelerated the canine movement (WMD: 0.72 mm; 95% CI = 0.63, 0.81 mm, P < 0.00001) compared to the traditional orthodontic group. The periodontally accelerated osteogenic orthodontic (PAOO) strategy markedly reduced the total treatment duration (SMD: -1.98; 95% CI = -2.59, -1.37, P < 0.00001) and increased the bone thickness (SMD:1.07; 95% CI = 0.74, 1.41, P < 0.00001) compared to traditional orthodontic treatment. CONCLUSION: The present study suggests that facilitated orthodontic treatment in terms of corticotomy and PAOO strategy may represent attractive and effective therapeutic strategy for orthodontic patients.

Recent Advances of Platinum-Based Anticancer Complexes in Combinational Multimodal Therapy.

Platinum drugs with manifest therapeutic effects are widely used, but their systemic toxicity and the drug resistance acquired by cancer cells limit their clinical applications. Thus, the exploration on appropriate methods and strategies to overcome the limitations of traditional platinum drugs becomes extremely necessary. Combination therapy of platinum drugs can inhibit tumor growth and metastasis in an additive or synergistic manner, and can potentially reduce the systemic toxicity of platinum drugs and overcome platinum-resistance. This review summarizes the various modalities and current progress in platinum-based combination therapy. The synthetic strategies and therapeutic effects of some platinum-based anticancer complexes in the combination of platinum drugs with gene editing, ROS-based therapy, thermal therapy, immunotherapy, biological modelling, photoactivation, supramolecular self-assembly and imaging modality are briefly described. Their potential challenges and prospects are also discussed. It is hoped that this review will inspire researchers to have more ideas for the future development of highly effective platinum-based anti-cancer complexes.

Perception Research of Artificial Intelligence in Environmental Public Health Physiotherapy Nursing for the Elderly.

This perceptual study focuses on developing artificial intelligence for elderly care design. It analyses and discusses the role of artificial intelligence in elderly care and its application to physiotherapy care. Artificial intelligence, as an emerging disruptive technology, is releasing the enormous energy accumulated in the technological and industrial revolutions, profoundly transforming how humans produce, live, and think about the world. Economic development and social progress are significantly impacted by it, and it has a great deal of practicality and broad application scope. Although there is a basic consensus in the 18 public understanding of AI, there is still some ambiguity and misunderstanding, knowing what is happening without understanding why. As a result, it is necessary to systematize and gain a comprehensive understanding of this concept and its associated practices.

A red-light activatable and mitochondrion-targeting PtIV complex to overcome drug resistance.

The therapeutic effects of platinum anticancer drugs are commonly whittled away by drug resistance, which is associated with drug efflux and the nucleotide excision repair (NER) pathway. Activation of drugs in a spatiotemporally controllable manner in the mitochondria of cancer cells is a very promising strategy to alleviate these problems. In this work, PtIV-PS2, a cisplatin-based PtIV prodrug, was designed to release cisplatin inside the mitochondria on red light exposure. This PtIV complex could be effectively reduced to PtII species under irradiation. PtIV-PS2 very effectively accumulates in the mitochondria of cancer cells through active transport. After photoactivation, PtIV-PS2 showed higher cytotoxicity than cisplatin in the cisplatin-resistant carcinoma cells and the amount of Pt in genomic DNA was elevated. Moreover, PtIV-PS2 decreased the cellular mitochondrial membrane potential (MMP) and the cellular content of ATP. This work developed a promising window for the design of controllably activated and mitochondrion-targeting PtIV prodrugs to overcome drug resistance of chemotherapy.

Influence of nanoparticle size on blood-brain barrier penetration and the accumulation of anti-seizure medicines in the brain.

Anti-seizure medicines constitute a common yet important modality to treat epilepsy. However, some of them are associated with serious side effects including hepatotoxicity and hypersensitivity. Furthermore, the blood-brain barrier (BBB) is an insurmountable obstacle for brain drug delivery. Fortunately, the introduction of the nanoparticles for drug delivery is a feasible approach to overcome these obstacles. Encapsulating drugs into nanoparticles and delivering them to specific sites shows great potential for improving the efficiency of drug delivery and reducing systemic toxicity. Several in vivo studies have investigated the effect of nanoparticle size on biodistribution in mice, but very few have investigated its effects on efficient drug delivery while crossing the BBB. Therefore, we designed a methoxy poly(lactide-co-glycolide)-b-poly(ethylene glycol) methyl ether (mPEG-PLGA) nanoparticle delivery system and explored the cell uptake efficiency of nanoparticles with different sizes and their ability to penetrate the BBB while carrying carbamazepine (CBZ). CBZ-loaded nanoparticles could significantly reduce the cytotoxicity of CBZ to L929 cells at high concentrations. Results from the endocytosis experiment involving human cerebral microvessel endothelial cell/D3 showed that the DiR-loaded mPEG5K-PLGA10K nanoparticles possessed the highest cell uptake efficiency. The endocytosis efficiency was 90% at 30 min, which far exceeded that of the other groups. Moreover, similar results were obtained from subsequent experiments where fluorescence images of the isolated organs of the mice were acquired. To summarize, our study demonstrated that drug delivery to the brain using nanocarriers is size dependent. Nanoparticles with the smallest particle size can be internalized more effectively, and easily penetrate the BBB, and accumulate in the brain.

Clinical Reference Strategy for the Selection of Treatment Materials for Maxillofacial Bone Transplantation: A Systematic Review and Network Meta-Analysis.

Bone graft materials have mixed effects of bone repair in the field of oral maxillofacial surgery. The qualitative analyses performed by previous studies imply that autogenous odontogenic materials and autogenous bone have similar effects on bone repair in clinical jaw bone transplantation. This retrospective systematic assessment and network meta-analysis aimed to analyze the best effect of clinical application of autogenous odontogenic materials and autogenous, allogeneic, and xenogeneic bone grafts in bone defect repair. A systematic review was performed by searching the PubMed, Cochrane Library, and other journal databases using selected keywords and Medical Subject Headings search terms. 10 Papers (n = 466) that met the inclusion criteria were selected. The assessment of heterogeneity did not reveal any overall statistical difference or heterogeneity (P = 0.051 > 0.05), whereas the comparison between autogenous and allogeneic bone grafts revealed local heterogeneity (P = 0.071 < 0.1). Risk of bias revealed nine unclear studies and one high-risk study. The overall consistency was good (P = 0.065 > 0.05), and the local inconsistency test did not reveal any inconsistency. The publication bias was good. The confidence regarding the ranking of bone graft materials after GRADE classification was moderate. The effects on bone repair in the descending order were as follows: autogenous odontogenic materials, xenogeneic bone, autogenous bone, and allogeneic bone. This result indicates that the autogenous odontogenic materials displayed stronger effects on bone repair compared to other bone graft materials. Autogenous odontogenic materials have broad development prospects in oral maxillofacial surgery.

Synergistic enhancement of immunological responses triggered by hyperthermia sensitive Pt NPs via NIR laser to inhibit cancer relapse and metastasis.

The combination of tumor ablation and immunotherapy is a promising strategy against tumor relapse and metastasis. Photothermal therapy (PTT) triggers the release of tumor-specific antigens and damage associated molecular patterns (DAMPs) in-situ. However, the immunosuppressive tumor microenvironment restrains the activity of the effector immune cells. Therefore, systematic immunomodulation is critical to stimulate the tumor microenvironment and augment the anti-tumor therapeutic effect. To this end, polyethylene glycol (PEG)-stabilized platinum (Pt) nanoparticles (Pt NPs) conjugated with a PD-L1 inhibitor (BMS-1) through a thermo-sensitive linkage were constructed. Upon near-infrared (NIR) exposure, BMS-1 was released and maleimide (Mal) was exposed on the surface of Pt NPs, which captured the antigens released from the ablated tumor cells, resulting in the enhanced antigen internalization and presentation. In addition, the Pt NPs acted as immune adjuvants by stimulating dendritic cells (DCs) maturation. Furthermore, BMS-1 relieved T cell exhaustion and induced the infiltration of effector T cells into the tumor tissues. Thus, Pt NPs can ablate tumors through PTT, and augment the anti-tumor immune response through enhanced antigen presentation and T cells infiltration, thereby preventing tumor relapse and metastasis.

Dual-sensitive dual-prodrug nanoparticles with light-controlled endo/lysosomal escape for synergistic photoactivated chemotherapy.

The clinical application of conventional chemotherapeutic agents, represented by cisplatin, is limited by severe side effects. So, it is essential to explore more safer and controlled drug delivery systems for synergistic chemotherapy. In this work, we designed dual-sensitive dual-prodrug nanoparticles (DDNPs) for photoactivated platinum-based synergistic chemotherapy. With photosensitivity, DDNPs could be photoactivated from inert Pt(IV) to toxic Pt(II) under safe UVA light in a spatiotemporally controlled manner. Concurrently, mild could be generated from DDNPs to assist the endo/lysosomal escape of DDNPs for better photoactivated chemotherapy (PACT). Furthermore, with acid-sensitivity, demethylcantharidin (DMC), a protein phosphatase 2A (PP2A) inhibitor, was released to block the DNA repair pathway and thereby could sensitize platinum-based chemotherapy in intracellular acidic microenvironments. Along with a precise ratio (Pt : DMC = 1 : 2), DDNPs had a powerful synergistic anti-cancer effect in vitro and in vivo. In the future, DDNPs have great potential as a safe and multifunctional drug delivery system for precise nanomedicine in clinical treatments.

Comparison of Autogenous Tooth Materials and Other Bone Grafts.

Autogenous odontogenic materials are a new, highly biocompatible option for jaw restoration. The inorganic component of autogenous teeth acts as a scaffold to maintain the volume and enable donor cell attachment and proliferation; the organic component contains various growth factors that promote bone reconstruction and repair. The composition of dentin is similar to that of bone, which can be a rationale for promoting bone reconstruction. Recent advances have been made in the field of autogenous odontogenic materials, and studies have confirmed their safety and feasibility after successful clinical application. Autogenous odontogenic materials have unique characteristics compared with other bone-repair materials, such as the conventional autogenous, allogeneic, xenogeneic, and alloplastic bone substitutes. To encourage further research into odontogenic bone grafts, we compared the composition, osteogenesis, and development of autogenous odontogenic materials with those of other bone grafts. In conclusion, odontogenic bone grafts should be classified as a novel bone substitute.

Effects of Physical Stimulation in the Field of Oral Health.

Physical stimulation has been widely used in clinical medicine and healthcare due to its noninvasiveness. The main applications of physical stimulation in the oral cavity include laser, ultrasound, magnetic field, and vibration, which have photothermal, cavitation, magnetocaloric, and mechanical effects, respectively. In addition, the above four stimulations with their unique biological effects, which can play a role at the gene, protein, and cell levels, can provide new methods for the treatment and prevention of common oral diseases. These four physical stimulations have been used as important auxiliary treatment methods in the field of orthodontics, implants, periodontal, dental pulp, maxillofacial surgery, and oral mucosa. This paper systematically describes the application of physical stimulation as a therapeutic method in the field of stomatology to provide guidance for clinicians. In addition, some applications of physical stimulation in specific directions are still at the research stage, and the specific mechanism has not been fully elucidated. To encourage further research on the oral applications of physical stimulation, we elaborate the research results and development history of various physical stimuli in the field of oral health.

A portable fast neutron irradiation system for tumor therapy.

A portable neutron tube was introduced as a small-sized (weight≤14.4 kg, power consumption ≤50W and cost≤ $100,000) neutron accelerator and applied for irradiation therapy on cancer. The effect of growth-inhibiting in vitro by neutrons irradiation on HeLa cells (human cervical cancer cells) was evaluated by colony formation assays, and cell apoptosis was evaluated by Flow Cytometry. A polyethylene protection device as the neutron moderator was designed and connected to the neutron tube to shield normal tissue and organs of the test animals from scatter radiation. Hematology and blood biochemistry were investigated to evaluate the protective effect of polyethylene. U14 (mice cervical cancer cell) tumor-bearing mice were further investigated to determine the tumor suppression effect of neutron irradiation. We found that cells showed a dose-dependent relationship after fast neutrons irradiation at different dose (1.11 Gy, 2.23 Gy, 3.34 Gy and 4.45Gy). Furthermore, in vivo experiments showed that the anti-tumor effect on U14 tumor-bearing mice greatly depended on the neutron irradiation dose. A high dose of fast neutron irradiation (26.73 Gy) could have tumor growth rate only 12.31% compared to 56.07% with control group. All the blood cell counts and blood biochemistry parameters were in the standard value ranges. Immunohistochemistry examinations clearly indicated the apoptosis cells in tumor tissues by the TUNEL assay. This work provides useful evidences on cancer irradiation therapy using fast neutron in pre-clinical study. And the neutron therapy system device has great potential to be a more convenient tool in clinical application with significantly lower power consumption, irradiation toxicity and cost.

Photoactivated polyprodrug nanoparticles for effective light-controlled Pt(iv) and siRNA codelivery to achieve synergistic cancer therapy.

Endo/lysosomal escape and the subsequent controllable/precise release of drugs and genes are key challenges for efficient synergistic cancer therapy. Herein, we report a photoactivated polyprodrug nanoparticle system (PPNPsiRNA) centered on effective light-controlled codelivery of Pt(iv) prodrug and siRNA for synergistic cancer therapy. Under green-light irradiation, PPNPsiRNA can sustainedly generate oxygen-independent azidyl radicals to facilitate endo/lysosomal escape through the photochemical internalization (PCI) mechanism. Besides, concurrent Pt(ii) release and siRNA unpacking could occur in a controllable manner after the decomposition of Pt(iv), main chain shattering of photoactivated polyprodrug and the PPNPsiRNA disassociation. Based on these innovative features, excellent synergistic therapeutic efficacy of chemo- and RNAi therapies of PPNPsiBcl-2 could be achieved on ovarian cancer cells under light irradiation. The facile synthesized and prepared photoactivatable polyprodrug nanoparticle system provides a new strategy for effective gene/drug codelivery, where controllable endo/lysosomal escape and the subsequent drug/gene release/unpacking play vital roles, which could be adopted as a versatile codelivery nanoplatform for the treatment of various cancers.