Dried tangerine peel polysaccharide (DTPP) alleviates hepatic steatosis by suppressing TLR4/MD-2-mediated inflammation and endoplasmic reticulum stress.

Non-alcoholic fatty liver disease (NAFLD) is a complex pathogenic metabolic syndrome characterized by increased inflammation and endoplasmic reticulum stress. In recent years, natural polysaccharides derived from traditional Chinese medicine have shown significant anti-inflammatory effects, making them an attractive therapeutic option. However, little research has been conducted on the therapeutic potential of dried tangerine peel polysaccharide (DTPP) - one of the most important medicinal resources in China. The results of the present study showed that DTPP substantially reduced macrophage infiltration in vivo and suppressed the expression of pro-inflammatory factors and endoplasmic reticulum stress-related genes. Additionally, surface plasmon resonance analysis revealed that DTPP had a specific affinity to myeloid differentiation factor 2, which consequently suppressed lipopolysaccharide-induced inflammation via interaction with the toll-like receptor 4 signaling pathway. This study provides a potential molecular mechanism underlying the anti-inflammatory effects of DTPP on NAFLD and suggests DTPP as a promising therapeutic strategy for NAFLD treatment.

Lian-Mei-Yin formula alleviates diet-induced hepatic steatosis by suppressing Yap1/FOXM1 pathway-dependent lipid synthesis.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with a global prevalence of 25%. Patients with NAFLD are more likely to suffer from advanced liver disease, cardiovascular disease, or type II diabetes. However, unfortunately, there is still a shortage of FDA-approved therapeutic agents for NAFLD. Lian-Mei-Yin (LMY) is a traditional Chinese medicine formula used for decades to treat liver disorders. It has recently been applied to type II diabetes which is closely related to insulin resistance. Given that NAFLD is another disease involved in insulin resistance, we hypothesize that LMY might be a promising formula for NAFLD therapy. Herein, we verify that the LMY formula effectively reduces hepatic steatosis in diet-induced zebrafish and NAFLD model mice in a time- and dose-dependent manner. Mechanistically, LMY suppresses Yap1-mediated Foxm1 activation, which is crucial for the occurrence and development of NAFLD. Consequently, lipogenesis is ameliorated by LMY administration. In summary, the LMY formula alleviates diet-induced NAFLD in zebrafish and mice by inhibiting Yap1/Foxm1 signaling-mediated NAFLD pathology.

Discovery of novel cannabidiol derivatives with augmented antibacterial agents against methicillin-resistant Staphylococcus aureus.

Drug-resistant bacterium infections are a severe threat to public health and novel antimicrobial agents combating drug-resistant bacteria are an unmet medical need. Although cannabidiol (CBD) has been reported to show antibacterial effects, whether its antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) can be improved remains unclear. Herein, a series of novel CBD derivatives were designed and synthesized using various chemical approaches including amidation, Friedel-Crafts alkylation, and Negishi cross-coupling reaction for the modifications at the C-7, C-2', C-4', and C-6' positions of CBD skeleton. Derivative 21f showed augmented antibacterial activity against MRSA with a minimum inhibitory concentration of 4 µM without cytotoxic effect in microglia BV2 cells. Further mechanistic studies suggested that 21f inhibited the formation of biofilms, induced excess reactive oxygen species, and reduced bacterial metabolism, which collectively led to the acceleration of bacterial death. Findings from this study expand the understanding of CBD derivatives as promising antibacterial agents, which provides useful information for the development of cannabinoid-based antibacterial agents.

Fucoidan from Fucus vesiculosus Inhibits Inflammatory Response, Both In Vitro and In Vivo.

Fucoidan has been reported to present diverse bioactivities, but each extract has specific features from which a particular biological activity, such as immunomodulation, must be confirmed. In this study a commercially available pharmaceutical-grade fucoidan extracted from Fucus vesiculosus, FE, was characterized and its anti-inflammatory potential was investigated. Fucose was the main monosaccharide (90 mol%) present in the studied FE, followed by uronic acids, galactose, and xylose that were present at similar values (3.8-2.4 mol%). FE showed a molecular weight of 70 kDa and a sulfate content of around 10%. The expression of cytokines by mouse bone-marrow-derived macrophages (BMDMs) revealed that the addition of FE upregulated the expression of CD206 and IL-10 by about 28 and 22 fold, respectively, in respect to control. This was corroborated in a stimulated pro-inflammatory situation, with the higher expression (60 fold) of iNOS being almost completely reversed by the addition of FE. FE was also capable of reverse LPS-caused inflammation in an in vivo mouse model, including by reducing macrophage activation by LPS from 41% of positive CD11C to 9% upon fucoidan injection. Taken together, the potential of FE as an anti-inflammatory agent was validated, both in vitro and in vivo.

A Water-Soluble, Two-Photon Probe for Imaging Endogenous Hypochlorous Acid in Live Tissue.

Detection of hypochlorous acid (HClO) in the living system may help to uncover its essential biological functions. However, current imaging agents suffer from poor water solubility that limit their live-tissue applications. Here, a water-soluble probe (NNH) is devised through innovative hydrazone modification of 1,8-naphthalimide at 3' position. NNH was successfully applied to tracking endogenous HClO in both cultured macrophages and a liver injury model in mice. NNH demonstrated remarkably increased water solubility and multiple desirable features including two-photon absorbance, anti-bleaching capability, rapid cellular uptake, and low cytotoxicity. NNH is the first hydrazone-based probe for real-time imaging of HClO in live tissue.

Dried tangerine peel polysaccharide accelerates wound healing by recruiting anti-inflammatory macrophages.

Macrophage polarization is a key process involved in wound healing. The continuous release of proinflammatory cytokines by macrophages inhibits the healing process of chronic wounds, such as diabetic wounds. To promote wound healing, it is important to change the phenotype of resident macrophages to prevent inflammation. We previously reported that dried tangerine peel polysaccharide (DTPP) binds to and inhibits the TLR4/MD-2 complex, which is crucial for the inflammatory activation of macrophages, suggesting the potential of DTPP in wound healing applications. Both zebrafish and mouse models were used to evaluate the therapeutic efficacy of DTPP. Moreover, we found that DTPP recruited macrophages to the wound area and promoted their M2 repolarization. Using hyperglycaemic zebrafish and db/db mouse models, we discovered that DTPP accelerated wound healing in vivo in metabolic disorders. Our results suggest that DTPP promotes the recruitment of macrophages, shifts macrophages towards the anti-inflammatory M2 phenotype, and ultimately accelerates the wound healing process.

Comparative Study on the Mechanism of Macrophage Activation Induced by Polysaccharides from Fresh and Dried Longan.

Longan (Dimcarpus longan Lour.) is a kind of traditional fruit used as a medicine and a food. Fresh longan is primarily consumed as a fruit, whereas dried longan is commonly employed for medicinal purposes. The differences in the immunomodulatory activities and mechanisms of polysaccharides between dried and fresh longan remain unclear. The present study comparatively analyzed the mechanisms of macrophage activation induced by polysaccharides from dried (LPG) and fresh longan (LPX). The results revealed that LPG and LPX differentially promoted macrophage phagocytosis and the secretion of NO, TNF-α, and IL-6. RNA-seq analysis revealed that LPG and LPX differentially affected gene expression in macrophages. The LPG treatment identified Tnf and chemokine-related genes as core genes, while myd88 and interferon-related genes were the core genes affected by LPX. A comprehensive analysis of the differentially expressed genes showed that LPG initiated macrophage activation primarily through the TLR2/4-mediated TRAM/TRAF6 and CLR-mediated Src/Raf1 NF-κB signaling pathways. LPX initiated macrophage activation predominantly via the CLR-mediated Bcl10/MALT1 and NLR-mediated Rip2/TAK1 MAPK and NF-κB signaling pathways. Interestingly, the non-classical NF-κB signaling pathway was activated by polysaccharides in both dried and fresh longan to elicit a slow, mild immune response. LPG tends to promote immune cell migration to engage in the immune response, while LPX facilitates antigen presentation to promote T cell activation. These findings contribute insights into the mechanisms underlying the differences in bioactivity between dried and fresh longan and their potential applications in immune-enhancing strategies and functional-food development.

Bcl-xL Promotes the Survival of Motor Neurons Derived from Neural Stem Cells.

Neural stem cell (NSC) transplantation creates new hope for the treatment of neurodegenerative disorders by direct differentiation into neurons. However, this technique is limited by poor survival and functional neuron deficiency. In this research study, we generated pro-survival murine NSCs (mNSCs) via the ectopic expression of Bcl-xL. A doxycycline (Dox)-inducible Ngn2-Isl1-Lhx3 system was also integrated into the mNSC genome. The four gene-modified mNSCs can rapidly and effectively differentiate into motor neurons after Dox treatments. Ectopic Bcl-xL could resist replating-induced stress, glutamate toxicity, neuronal apoptosis and remarkably promote the survival of motor neurons. Taken together, we established genetically modified mNSCs with improved survival, which may be useful for motor neuron degenerative diseases.

Turning gray selenium into a nanoaccelerator of tissue regeneration by PEG modification.

Selenium (Se) is an essential trace element involved in nearly all human physiological processes but suffers from a narrow margin between benefit and toxicity. The nanoform of selenium has been proven shown to be more bioavailable and less toxic, yet significant challenges remain regarding the efficient and feasible synthesis of biologically active nanoselenium. In addition, although nanoselenium has shown a variety of biological activities, more interesting nanoselenium features are expected. In this work, hydrosoluble nanoselenium termed Nano-Se in the zero oxidation state was synthesized between gray Se and PEG. A zebrafish screen was carried out in zebrafish larvae cocultured with Nano-Se. Excitingly, Nano-Se promoted the action of the FGFR, Wnt, and VEGF signaling pathways, which play crucial roles in tissue regeneration. As expected, Nano-Se not only achieved the regeneration of zebrafish tail fins and mouse skin but also promoted the repair of skin in diabetic mice while maintaining a profitable safe profile. In brief, the Nano-Se reported here provided an efficient and feasible method for bioactive nanoselenium synthesis and not only expanded the application of nanoselenium to regenerative medicine but also likely reinvigorated efforts for discovering more peculiarunique biofunctions of nanoselenium in a great variety of human diseases.

Smectite promotes probiotic biofilm formation in the gut for cancer immunotherapy.

Administration of probiotics to regulate the immune system is a potential anti-tumor strategy. However, oral administration of probiotics is ineffective because of the poor inhabitation of exogenous bacteria in host intestines. Here we report that smectite, a type of mineral clay and established anti-diarrhea drug, promotes expansion of probiotics (especially Lactobacillus) in the murine gut and subsequently elicits anti-tumor immune responses. The ion-exchangeable microstructure of smectite preferentially promotes lactic acid bacteria (LABs) to form biofilms on smectite in vitro and in vivo. In mouse models, smectite laden with LAB biofilms (Lactobacillus and Bifidobacterium) inhibits tumor growth (when used alone) and enhances the efficacy of chemotherapy or immunotherapy (when used in combination with either of them) by activating dendritic cells (DCs) via Toll-like receptor 2 (TLR2) signaling. Our findings suggest oral administration of smectite as a promising strategy to enrich probiotics in vivo for cancer immunotherapy.

An "all-in-one" scaffold targeting macrophages to direct endogenous bone repair in situ.

Scaffolds for tissue repair are designed in an increasingly complicated manner to meet multi-facet biological needs during the healing process. However, overly sophisticated design, especially the use of multiple components and delivery of exogenous cells, hampers the bench-to-bedside translation. Here, a multi-functional - yet mono-compositional - bioactive scaffold is devised to mediate the full-range, endogenous bone repair. Based on immunoactivity screening, a chemically-modified glucomannan polysaccharide is selected and processed into an anisotropic porous scaffold, which accurately stimulates macrophages to produce pro-regenerative cytokines. These cytokines effectively enhance the recruitment ("R") and induced osteogenesis ("IO") of the bone progenitor cells in situ. Meanwhile, the anisotropic porosity and carbohydrate signal of the scaffold facilitate differential adhesion ("A") and distribution ("D") of the macrophages and bone progenitor cells - enabling the former's accumulation at the surface while encouraging the latter's infiltration into the scaffold. Implanted in a rat calvarial defect model, this "RADIO" system effectively promotes healing over 12 weeks, with the obvious formation of hard callus through the scaffold. In summary, RADIO integrates multiple functions into one single scalable system ("all-in-one") to govern the dynamic bone-repair process, by harnessing the power of host macrophages. RADIO represents an open platform to solving the long-lasting complexity-versus-simplicity dilemma in biomaterials design. STATEMENT OF SIGNIFICANCE: Biomaterials as versatile tools for tissue repair are becoming increasingly complicated, yet overly sophisticated design - especially the use of multiple components, exogenous cells, and overdosed growth factors - hampers their clinical application. The pre-requisite for designing a successful integrative scaffold is to identify an inherent biological target responding to biomaterial signals, thereby efficiently and safely promoting tissue repair via the endogenous healing capability instead of extra multifarious biochemical components. For bone regeneration, the pivotal regulator is macrophages. Through activating host macrophages, our single-component scaffold system coordinates the entire bone regenerative cascade in situ and induces successful bone regeneration in a calvarial defect model. This scaffold represents a scalable and multi-functional approach to effectively simplify the sophisticated design in regenerative medicine.

A toll-like receptor agonist mimicking microbial signal to generate tumor-suppressive macrophages.

Switching macrophages from a pro-tumor type to an anti-tumor state is a promising strategy for cancer immunotherapy. Existing agents, many derived from bacterial components, have safety or specificity concerns. Here, we postulate that the structures of the bacterial signals can be mimicked by using non-toxic biomolecules of simple design. Based on bioactivity screening, we devise a glucomannan polysaccharide with acetyl modification at a degree of 1.8 (acGM-1.8), which specifically activates toll-like receptor 2 (TLR2) signaling and consequently induces macrophages into an anti-tumor phenotype. For acGM-1.8, the degree of acetyl modification, glucomannan pattern, and acetylation-induced assembly are three crucial factors for its bioactivity. In mice, intratumoral injection of acGM-1.8 suppresses the growth of two tumor models, and this polysaccharide demonstrates higher safety than four classical TLR agonists. In summary, we report the design of a new, safe, and specific TLR2 agonist that can generate macrophages with strong anti-tumor potential in mice.

An ortho-aldehyde modified probe to image thiols in living cells with enhanced selectivity.

Developing fluorescent probes to image thiols in the living system may provide powerful tools to study the functions of thiol-containing biological molecules. In this study, we report the design and evaluation of a novel turn-on fluorescent probe NQNO for selective detection of thiols in living cells. By introducing an ortho-aldehyde group to NNO, a conventional compound representing a class of thiol-imaging strategy, we obtained NQNO with enhanced selectivity for thiols over the major interferent hydrogen sulfide (H2S). NQNO could be applied in phosphate-buffered saline (PBS), where the efficacy of NNO was usually weakened. Notably, NQNO demonstrated solid performance in imaging endogenous thiols in living cells without exerting cytotoxicity. In summary, NQNO has the potential to serve as a safe, sensitive and effective fluorescent probe for thiol imaging in biological systems.

Post-screening characterisation and in vivo evaluation of an anti-inflammatory polysaccharide fraction from Eucommia ulmoides.

We report here the discovery of a polysaccharide, namely EUP1, with anti-inflammatory activity from the herb of Eucommia ulmoides Oliv. We separated three polysaccharide fractions from this herb based on acidity and screened them for their activity in modulating the phenotype of murine macrophages. Among them, EUP1 was the only fraction to exert such a function - it stimulated Raw 264.7 cells to express CD206 and a key anti-inflammatory cytokine interleukin-10. Having fully characterised EUP1 with a series of chromatographic and spectroscopic analyses, we evaluated its anti-inflammatory effects in both in vitro and in vivo inflammatory models. In the murine model of sepsis induced by lipopolysaccharide, administration of EUP1 effectively suppressed the expression of major inflammatory cytokines, alleviated lung injury and increased animal survival rate. In summary, EUP1, with a clearly elucidated chemical structure and solid anti-inflammatory activity, may become a valuable candidate for further development into an anti-septic therapeutic agent.

A tumour microenvironment-responsive polymeric complex for targeted depletion of tumour-associated macrophages (TAMs).

Tumour-associated macrophages (TAMs) play pivotal roles in promoting cancer progression. Systemic delivery of therapeutic agents to efficiently eliminate these cells remains challenging. Here, we report the development of a bio-responsive polymeric complex (P3AB) that can be systemically administrated to target and eliminate TAMs in tumours. This complex comprises a polymeric 'shell' and 'core'. The shell (PPP) consists of poly(ethylene glycol) (PEG), poly(lactic-co-glycolic acid) (PLGA), and a peptide that can be cleaved by matrix metalloproteases (MMPs) in the tumour microenvironment; and the 'core' (AB) is a bisphosphonate-glucomannan conjugate that has affinity for macrophage mannose receptors and selectively eliminates TAMs. Our data show that the P3AB complex can be accumulated in the tumour site thanks to its appropriate size and its PPP shell is sensitively cleaved by MMPs, efficiently releasing the AB core that can potently reduce TAM viability. The systemically delivered P3AB complex demonstrates favourable responses to the physiological features of the tumour microenvironment (e.g. underdeveloped vasculature and high MMP levels), and effectively inhibits tumour growth and restores local immunosurveillance in vivo, without exerting hepatotoxicity. Taken together, our findings suggest that P3AB has the potential to be an effective and safe tool for TAM-targeting cancer immunotherapy.

A macrophage-activating, injectable hydrogel to sequester endogenous growth factors for in situ angiogenesis.

Biomaterials scaffolds designed for many regenerative applications are expected to support neo-vascularisation, which is now being hampered by two limitations - the instability of exogenous growth factors (GFs) that are delivered to promote angiogenesis; and the loss of extracellular matrix components that bind and stabilise GFs. Here, we report the design and evaluation of an injectable hydrogel system aimed at restoring a GF-binding microenvironment to enhance the pro-angiogenic functions of endogenous GFs. This gel comprises two polysaccharides with their unique bioactivities: Konjac glucomannan (KGM) as the building block of the gel scaffold, for its demonstrated capacity to activate macrophages/monocytes to secrete pro-angiogenic/-mitogenic GFs; and heparin (Hep), a representative glycosaminoglycan molecule that binds numerous pro-angiogenic GFs, as functional moieties to sequester the macrophage-produced GFs. Modified with tyramine (TA) groups, the two polysaccharides can be co-polymerised and rapidly form into hydrogel upon enzyme catalysis. The designed KGM-TA/Hep-TA hydrogel successfully preserves the macrophage-activating function and GF-binding affinity of the two components, respectively, and, once subcutaneously implanted, effectively sequestered the locally-produced GFs in situ and promote the formation and maturation of blood vessels in mice. In summary, the designed hydrogel system demonstrates a feasible approach to stimulate the production and harness the function of endogenous GFs for inducing blood vessel formation in vivo, without the addition of any exogenous proteins. This design may provide an innovative, open platform to promote vascularisation for various regenerative purposes.

Functionalized Multiwalled Carbon Nanotubes as Carriers of Ruthenium Complexes to Antagonize Cancer Multidrug Resistance and Radioresistance.

Multidrug resistance and radioresistance are major obstacles for successful cancer therapy. Due to the unique characteristics of high surface area, improved cellular uptake, and the possibility to be easily bound with therapeutics, carbon nanotubes (CNTs) have attracted increasing attention as potential nanodrug delivery systems. In this study, a CNT-based radiosensitive nanodrug delivery system was rationally designed to antagonize the multidrug resistance in hepatocellular carcinoma. The nanosystem was loaded with a potent anticancer ruthenium polypyridyl complex (RuPOP) via π-π interaction and formation of a hydrogen bond. The functionalized nanosystem (RuPOP@MWCNTs) enhanced the cellular uptake of RuPOP in liver cancer cells, especially drug-resistant R-HepG2 cells, through endocytosis. Consistently, the selective cellular uptake endowed the nanosystem amplified anticancer efficacy against R-HepG2 cells but not in normal cells. Interestingly, RuPOP@MWCNTs significantly enhanced the anticancer efficacy of clinically used X-ray against R-HepG2 cells through induction of apoptosis and G0/G1 cell cycle arrest, with the involvement of ROS overproduction, which activated several downstream signaling pathways, including DNA damage-mediated p53 phosphorylation, activation of p38, and inactivation of AKT and ERK. Moreover, the nanosystem also effectively reduces the toxic side effects of loaded drugs and prolongs the blood circulation in vivo. Taken together, the results demonstrate the rational design of functionalized carbon nanotubes and their application as effective nanomedicine to overcome cancer multidrug resistance.

Differential effects of amino acid surface decoration on the anticancer efficacy of selenium nanoparticles.

The use of selenium for anticancer therapy has been heavily explored during the last decade. Amino acids (AAs) play central roles both as building blocks of proteins and intermediates in metabolism. In the present study, AAs-modified selenium nanoparticles (SeNPs@AAs) have been successfully synthesized in a simple redox system. Typical neutral (valine), acidic (aspartic acid) and basic (lysine) amino acids were used to decorate SeNPs, and the stable and homodisperse nanoparticles were characterized by zeta potential and transmission electron microscope. The result of X-ray photoelectron spectra (XPS) showed that the interaction of -NH3(+) groups of the amino acids with negative-charged SeNPs could be a driving force for dispersion of the nanoparticles. The screening of in vitro anticancer activities demonstrated that SeNPs@AAs exhibited differential growth inhibitory effects on various human cancer cell lines. Among them, SeNPs decorated by Lys displayed higher anticancer efficacy than those of valine and aspartic acid. The studies on the in vitro cellular uptake mechanisms revealed that SeNPs@AAs were internalized by cancer cells through endocytosis. Flow cytometric analysis and the determination of caspase activity indicated that treatment of the MCF-7 breast adenocarcinoma cells with SeNPs@AAs led to a dose-dependent increase in apoptosis. Moreover, it was found that SeNPs@AAs-induced ROS overproduction could be the upstream signal of caspase activation and mitochondrial dysfunction in cancer cells. Taken together, our results suggest that these amino acid biocompatible nanoparticles might have potential application as chemopreventive and chemotherapeutic agents for human cancers.

Mixed-ligand ruthenium polypyridyl complexes as apoptosis inducers in cancer cells, the cellular translocation and the important role of ROS-mediated signaling.

Ruthenium (Ru) polypyridyl complexes have emerged as leading players among the potential metal-based candidates for cancer treatment. However, the roles of cellular translocation in their action mechanisms remain elusive. Herein we present the synthesis and characterization of a series of ruthenium (Ru) complexes containing phenanthroline derivatives with varying lipophilicities, and examine their mechanism of anticancer action. Results showed that increasing the lipophilicity of complexes can enhance the rates of cellular uptake. The in vitro anticancer efficacy of these complexes depended on the levels of ROS overproduction, rather than on cellular Ru uptake levels. The introduction of a phenolic group on the ligand effectively enhanced their intracellular ROS generation and anticancer activities. In particular, complex 4, with an ortho-phenolic group on the ligand, exhibited better selectivity between cancer and normal cells in comparison with cisplatin. Notably, complex 4 entered the cancer cells partially through transferrin receptor-mediated endocytosis, and then it translocated from lysosomes to the mitochondria, where it activated mitochondrial dysfunction by regulation of Bcl-2 family proteins, thus leading to intracellular ROS overproduction. Excess ROS amplified apoptotic signals by activating many downstream pathways such as p53 and MAPK pathways to promote cell apoptosis. Overall, this study provides a drug design strategy for discovery of Ru-based apoptosis inducers, and elucidates the intracellular translocation of these complexes.

pH-responsive cancer-targeted selenium nanoparticles: a transformable drug carrier with enhanced theranostic effects.

Selenium nanoparticles (SeNPs) have been widely used in various biomedical applications, including cancer therapy, diagnosis and drug delivery. Herein, we fabricated a novel type of structure-transformable capsules by decoration of SeNPs with folate-chitosan to form smart-shell nanocapsules (FAC@CurP-SeNPs). The shrink particles could target cancer cells over expressing folate receptor and enter the cells via folate receptor-mediated endocytosis. FAC@CurP-SeNPs were expanded to snowflake particles under acidifying stimulus (pH 5.3), which led to enhanced drug-release over prolonged periods. Treatment with FAC@CurP-SeNPs significantly inhibited the growth of MCF-7 human breast carcinoma cells through induction of apoptosis, which was evidenced by accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation. The contribution of extrinsic and intrinsic apoptotic pathways to the cell apoptosis was confirmed by activation of caspase-9 and caspase-8. Internalized FAC@CurP-SeNPs triggers intracellular ROS overproduction, thus activates p53, MAPKs pathways and inhibits NFκB and to promote cell apoptosis. Our results suggest that FAC@CurP-SeNPs may be a candidate for further evaluation as a agent for human cancers, and the strategy to use transformable nanocapsules could be a highly efficient way to enhance controlled drug release and anticancer efficacy.