Frontier knowledge and future directions of programmed cell death in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common renal malignancies of the urinary system. Patient outcomes are relatively poor due to the lack of early diagnostic markers and resistance to existing treatment options. Programmed cell death, also known as apoptosis, is a highly regulated and orchestrated form of cell death that occurs ubiquitously throughout various physiological processes. It plays a crucial role in maintaining homeostasis and the balance of cellular activities. The combination of immune checkpoint inhibitors plus targeted therapies is the first-line therapy to advanced RCC. Immune checkpoint inhibitors(ICIs) targeted CTLA-4 and PD-1 have been demonstrated to prompt tumor cell death by immunogenic cell death. Literatures on the rationale of VEGFR inhibitors and mTOR inhibitors to suppress RCC also implicate autophagic, apoptosis and ferroptosis. Accordingly, investigations of cell death modes have important implications for the improvement of existing treatment modalities and the proposal of new therapies for RCC. At present, the novel modes of cell death in renal cancer include ferroptosis, immunogenic cell death, apoptosis, pyroptosis, necroptosis, parthanatos, netotic cell death, cuproptosis, lysosomal-dependent cell death, autophagy-dependent cell death and mpt-driven necrosis, all of which belong to programmed cell death. In this review, we briefly describe the classification of cell death, and discuss the interactions and development between ccRCC and these novel forms of cell death, with a focus on ferroptosis, immunogenic cell death, and apoptosis, in an effort to present the theoretical underpinnings and research possibilities for the diagnosis and targeted treatment of ccRCC.

Enhancing the tumor penetration of multiarm polymers by collagenase modification.

Tumor penetration is a critical determinant of the therapy efficacy of nanomedicines. However, the dense extracellular matrix (ECM) in tumors significantly hampers the deep penetration of nanomedicines, resulting in large drug-untouchable areas and unsatisfactory therapy efficacy. Herein, we synthesized a third-generation PAMAM-cored multiarm copolymer and modified the polymer with collagenase to enhance its tumor penetration. Each arm of the copolymer was a diblock copolymer of poly(glutamic acid)-b-poly(carboxybetaine), in which the polyglutamic acid block with abundant side groups was used to link the anticancer agent doxorubicin through the pH-sensitive acylhydrazone linkage, and the zwitterionic poly(carboxybetaine) block provided desired water solubility and anti-biofouling capability. The collagenase was conjugated to the ends of the arms via the thiol-maleimide reaction. We demonstrated that the polymer-bound collagenase could effectively catalyze the degradation of the collagen in the tumor ECM, and consequently augmented the tumor penetration and antitumor efficacy of the drug-loaded polymers.

Factors contributing to emotional distress when caring for children with imperforate anus: a multisite cross-sectional study in China.

Background: Imperforate anus (IA) has a life-long impact on patients and their families. The caregivers of children with IA (CoCIA) might experience distress, which could be detrimental to them physically and mentally. However, there are limitations in the related studies. This study aimed to investigate the prevalence of IA and the associated factors contributing to the distress experienced by CoCIA. Methods: A cross-sectional study was conducted in three tertiary children's hospitals from November 2018 to February 2019. Distress was assessed using the Chinese version of the Kessler Psychological Distress Scale, and possible determinants were assessed by the Caregiver Reaction Assessment, the Parent Stigma Scale, the Parent Perception of Uncertainty Scale, and the Social Support Scale. Demographic and clinical information was also collected. Multiple regression analysis was performed to explore the association between variables. Results: Out of 229 CoCIA, 52.9% reported experiencing a high level of distress or above. The data analysis revealed that health problems associated with caregiving, stigma, uncertainty, social support, and children who underwent anal reconstruction surgery 1 year before or earlier could significantly predicate caregivers' distress, and these factors could explain 50.1% of the variance. Conclusions: The majority of the caregivers of children with IA experience high levels of distress, particularly when their children undergo anal reconstruction surgery 1 year before or earlier. Additionally, health problems related to caregiving, stigma, uncertainty, and low social support could significantly predicate caregivers' distress. It is important for clinical staff to be aware of the prevalent situation of caregivers' distress and to make targeted interventions focused on addressing modifiable factors that should be carried out in family-based care.

Afterglow/Photothermal Bifunctional Polymeric Nanoparticles for Precise Postbreast-Conserving Surgery Adjuvant Therapy and Early Recurrence Theranostic.

Adjuvant whole-breast radiotherapy is essential for breast cancer patients who adopted breast-conserving surgery (BCS) to reduce the risk of local recurrences, which however suffer from large-area and highly destructive ionizing radiation-induced adverse events. To tackle this issue, an afterglow/photothermal bifunctional polymeric nanoparticle (APPN) is developed that utilizes nonionizing light for precise afterglow imaging-guided post-BCS adjuvant second near-infrared (NIR-II) photothermal therapy. APPN consists of a tumor cell targeting afterglow agent, which is doped with a NIR dye as an afterglow initiator and a NIR-II light-absorbing semiconducting polymer as a photothermal transducer. Such a design realizes precise afterglow imaging-guided NIR-II photothermal ablation of minimal residual breast tumor foci after BCS, thus achieving complete inhibition of local recurrences. Moreover, APPN enables early diagnosis and treatment of local recurrence after BCS. This study thus provides a nonionizing modality for precision post-BCS adjuvant therapy and early recurrence theranostic.

Sono-Driven STING Activation using Semiconducting Polymeric Nanoagonists for Precision Sono-Immunotherapy of Head and Neck Squamous Cell Carcinoma.

Immunotherapy has offered new opportunities to treat head and neck squamous cell carcinoma (HNSCC); however, its clinical applications are hindered by modest therapeutic outcomes and the "always-on" pharmacological activity of immunomodulatory agents. Strategies for precise spatiotemporal activation of antitumor immunity can tackle these issues but remain challenging. Herein, a semiconducting polymeric nanoagonist (SPNM) with in situ sono-activatable immunotherapeutic effects for precision sono-immunotherapy of HNSCC is reported. SPNM is self-assembled from a sonodynamic semiconducting polymer core conjugated with a stimulator of interferon genes (STING) agonist (MSA-2) via a singlet oxygen cleavable linker. Under sono-irradiation, SPNM produces singlet oxygen not only to eradicate tumor cells to trigger immunogenic cell death but also to unleash caged STING agonists via the cleavage of diphenoxyethene bonds for in situ activation of the STING pathway in the tumor region. Such sono-driven STING activation mediated by SPNM promotes effector T cell infiltration and potentiates systemic antitumor immunity, eventually leading to tumor growth inhibition and long-term immunological memory. This study thus presents a promising strategy for the precise spatiotemporal activation of cancer immunotherapy.

Fluoropolymer-MOF Hybrids with Switchable Hydrophilicity for 19F MRI-Monitored Cancer Therapy.

Cancer theranostics that combines cancer diagnosis and therapy is a promising approach for personalized cancer treatment. However, current theranostic strategies suffer from low imaging sensitivity for visualization and an inability to target the diseased tissue site with high specificity, thus hindering their translation to the clinic. In this study, we have developed a tumor microenvironment-responsive hybrid theranostic agent by grafting water-soluble, low-fouling fluoropolymers to pH-responsive zeolitic imidazolate framework-8 (ZIF-8) nanoparticles by surface-initiated RAFT polymerization. The conjugation of the fluoropolymers to ZIF-8 nanoparticles not only allows sensitive in vivo visualization of the nanoparticles by 19F MRI but also significantly prolongs their circulation time in the bloodstream, resulting in improved delivery efficiency to tumor tissue. The ZIF-8-fluoropolymer nanoparticles can respond to the acidic tumor microenvironment, leading to progressive degradation of the nanoparticles and release of zinc ions as well as encapsulated anticancer drugs. The zinc ions released from the ZIF-8 can further coordinate to the fluoropolymers to switch the hydrophilicity and reverse the surface charge of the nanoparticles. This transition in hydrophilicity and surface charge of the polymeric coating can reduce the "stealth-like" nature of the agent and enhance specific uptake by cancer cells. Hence, these hybrid nanoparticles represent intelligent theranostics with highly sensitive imaging capability, significantly prolonged blood circulation time, greatly improved accumulation within the tumor tissue, and enhanced anticancer therapeutic efficiency.

Tumor-targeting semiconducting polymer nanoparticles: efficient adjuvant photothermal therapy using ultra-low laser power inhibits recurrences after breast-conserving surgery.

The need for adjuvant therapy to inhibit local recurrence after breast-conserving surgery with minimal side effects is great. Adjuvant photothermal therapy (aPTT) has the potential to replace radiotherapy and eliminates its inherent damage to healthy tissues. Herein, we functionalized semiconducting polymer nanoparticles (SPNs) with cRGD-peptide and silicon 2,3-naphthalocyanine bis(trihexylsilyloxide) (NIR775) to target breast cancer and perform aPTT under an ultra-low laser power (0.2 W cm-2) after breast-conserving surgery (BCS). The synthesized RGD-SPNNIR775 showed an excellent photothermal conversion efficiency and biocompatibility and was demonstrated to accumulate in tumors specifically. The BCS could be performed with confidence under the guidance of preoperative and postoperative fluorescence imaging. Notably, the aPTT completely inhibited the local recurrence after the BCS without compromising the cosmetic effect of the BCS. These results indicate the prospect of RGD-SPNNIR775 as a theranostic nanoplatform for efficient aPTT using an ultra-low laser power to control recurrence after BCS.

Light-Driven Self-Recruitment of Biomimetic Semiconducting Polymer Nanoparticles for Precise Tumor Vascular Disruption.

Tumor vascular disrupting therapy has offered promising opportunities to treat cancer in clinical practice, whereas the overall therapeutic efficacy is notably limited due to the off-target effects and repeated dose toxicity of vascular disrupting agents (VDAs). To tackle this problem, a VDA-free biomimetic semiconducting polymer nanoparticle (SPNP ) is herein reported for precise tumor vascular disruption through two-stage light manipulation. SPNP consists of a semiconducting polymer nanoparticle as the photothermal agent camouflaged with platelet membranes that specifically target disrupted vasculature. Upon the first photoirradiation, SPNP administered in vivo generates mild hyperthermia to trigger tumor vascular hemorrhage, which activates the coagulation cascade and recruits more SPNP to injured blood vessels. Such enhanced tumor vascular targeting of photothermal agents enables intense hyperthermia to destroy the tumor vasculature during the second photoirradiation, leading to complete tumor eradication and efficient metastasis inhibition. Intriguingly, the mechanism study reveals that this vascular disruption strategy alleviates splenomegaly and reverses the immunosuppressive tumor microenvironment by reducing myeloid-derived suppressor cells. Therefore, this study not only illustrates a light-driven self-recruitment strategy to enhance tumor vascular disruption via a single dose of biomimetic therapeutics but also deciphers the immunotherapeutic role of vascular disruption therapy that is conducive to clinical studies.

Organic phosphorescent nanoscintillator for low-dose X-ray-induced photodynamic therapy.

X-ray-induced photodynamic therapy utilizes penetrating X-rays to activate reactive oxygen species in deep tissues for cancer treatment, which combines the advantages of photodynamic therapy and radiotherapy. Conventional therapy usually requires heavy-metal-containing inorganic scintillators and organic photosensitizers to generate singlet oxygen. Here, we report a more convenient strategy for X-ray-induced photodynamic therapy based on a class of organic phosphorescence nanoscintillators, that act in a dual capacity as scintillators and photosensitizers. The resulting low dose of 0.4 Gy and negligible adverse effects demonstrate the great potential for the treatment of deep tumours. These findings provide an optional route that leverages the optical properties of purely organic scintillators for deep-tissue photodynamic therapy. Furthermore, these organic nanoscintillators offer an opportunity to expand applications in the fields of biomaterials and nanobiotechnology.

Biomedical polymers: synthesis, properties, and applications.

Biomedical polymers have been extensively developed for promising applications in a lot of biomedical fields, such as therapeutic medicine delivery, disease detection and diagnosis, biosensing, regenerative medicine, and disease treatment. In this review, we summarize the most recent advances in the synthesis and application of biomedical polymers, and discuss the comprehensive understanding of their property-function relationship for corresponding biomedical applications. In particular, a few burgeoning bioactive polymers, such as peptide/biomembrane/microorganism/cell-based biomedical polymers, are also introduced and highlighted as the emerging biomaterials for cancer precision therapy. Furthermore, the foreseeable challenges and outlook of the development of more efficient, healthier and safer biomedical polymers are discussed. We wish this systemic and comprehensive review on highlighting frontier progress of biomedical polymers could inspire and promote new breakthrough in fundamental research and clinical translation.

A Sub-6 nm MnFe2O4-dichloroacetic acid nanocomposite modulates tumor metabolism and catabolism for reversing tumor immunosuppressive microenvironment and boosting immunotherapy.

Adenosine and lactate accumulated in tumor microenvironment are two major causes of immunosuppression, their concurrent downregulation holds promise in effective cancer immunotherapy, but remains challenging. Here, a sub-6 nm MnFe2O4 conjugated with dichloroacetic acid (DCA) nanoparticle is developed to modulate tumor glucose metabolism and ATP catabolism for reversing the tumor immunosuppressive microenvironment. The ultrasmall MnFe2O4-DCA nanoparticle can efficiently enter mitochondria and supply oxygen, improving the bioactivity of DCA to regulate glucose metabolism and reduce lactate production ca. 100 times higher than free DCA itself. Moreover, this design significantly downregulates CD39 and CD73 expression than DCA or MnFe2O4 alone, which consequently decreases the extracellular ATP catabolism. The concurrent regulation of glucose metabolism and ATP catabolism leads to increased immunostimulatory ATP level and decreased immunosuppressive adenosine and lactate levels in tumor microenvironment, eventually amplified dendritic cells maturation, enhanced cytotoxic T lymphocyte response, and improved cancer immunotherapy efficacy.

Analysis of edible characteristics, antioxidant capacities, and phenolic pigment monomers in Lilium bulbs native to China.

Lilium is cherished for its health-promoting properties in China. The bulbs of Lilium are rich in phenolic compounds, which are associated with antioxidant capacity. However, no systematic evaluation on phenolic compositions and antioxidant capacities for the edible Lilium native to China has been conducted. Herein, bulbs of 56 wild populations and three cultivars were collected. Their edible characteristics, antioxidant capacities, and pigments have been investigated and analyzed. The results showed that phenolic compounds contributed to the major colors (red, yellow and white) in Lilium bulbs. The seven phenolic pigment monomers responsible for the color of bulbs-cyanidin-3-O-rutinoside, isoquercitrin, regaloside B, regaloside C, regaloside H, regaloside A and regaloside D-were identified by the combination of HPLC-MS and NMR analysis. The population Lilium regale E. H. Wilson (Maoxian County, Sichuan Province) had the highest antioxidant capacity. According to the quantification results, Lilium bulbs with darker and redder colors possessed larger biomass, better nutrient compositions, significantly higher bioactive constituents, and higher antioxidant capacities than the three currently consumed cultivars of edible lily bulbs. Overall, these findings suggest that the mountainous area of southwest China could be the fourth source of edible lilies with the bulb-colored Lilium species.

Enhancing Penetration Ability of Semiconducting Polymer Nanoparticles for Sonodynamic Therapy of Large Solid Tumor.

Sonodynamic therapy (SDT) holds growing promise in deep-seated or large solid tumor treatment owing to its high tissue penetration depth ability; however, its therapeutic efficacy is often compromised due to the hypopermeable and hypoxic characteristics in the tumor milieu. Herein, a semiconducting polymer nanoparticle (SPNC) that synergistically enhances tumor penetration and alleviates tumor hypoxia is reported for sonodynamic therapy of large solid tumors. SPNC comprises a semiconducting polymer nanoparticle core as a sonodynamic converter coated with a poly (ethylene glycol) corona. An oxygen-modulating enzyme, catalase, is efficiently conjugated to the surface of nanoparticles via the coupling reaction. Superior to its counterpart SPNCs (SPNC2 (84 nm) and SPNC3 (134 nm)), SPNC with the smallest size (SPNC1 (35 nm)) can efficiently penetrate throughout the tumor interstitium to alleviate whole tumor hypoxia in a large solid tumor model. Upon ultrasound (US) irradiation, SPNC1 can remotely generate sufficient singlet oxygen to eradicate tumor cells at a deep-tissue depth. Such a single treatment of SPNC1-medicated sonodynamic therapy effectively inhibits tumor growth in a large solid tumor mouse model. Therefore, this study provides a generalized strategy to synergistically overcome both poor penetration and hypoxia of large tumors for enhanced cancer treatment.

Immune-regulating bimetallic metal-organic framework nanoparticles designed for cancer immunotherapy.

Immunogenic cell death (ICD) is a promising strategy in cancer immunotherapy to induce high immunogenicity and activate the immune system. However, its efficacy is counteracted by the concurrent exposure of phosphatidylserine (PS), an immunosuppressive signal on the surface of cancer cells. Here we report the synthesis of a bimetallic metal-organic framework (MOF) nanoparticle containing Gd3+ and Zn2+ (Gd-MOF-5) that can be used as an immunomodulator to downregulate the immunosuppressive PS signal and an ICD inducer to upregulate immunostimulatory signals. Gd3+ inhibits PS externalization via inhibiting the activity of scramblase, an enzyme to transfer PS to the outer leaflet of plasma membrane. Moreover, intracellular Zn2+ overload activates endoplasmic reticulum stress for ICD induction. In combination with an immune checkpoint inhibitor (PD-L1 antibody, denoted as aPDL1), Gd-MOF-5 activated potent immune response and effectively inhibited primary and distal tumor growth in a bilateral 4T1 tumor model. This work presents a new strategy using designed MOF materials to modulate the cell signalling and immunosuppressive microenvironment to improve the outcome of cancer immunotherapy.

Plasma Interleukin-6 Level: A Potential Prognostic Indicator of Emergent HBV-Associated ACLF.

Objective: To identify markers that predict the progression to hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Methods: We recruited 125 patients with chronic hepatitis B (CHB) between September 2013 and March 2017. During hospitalization, 25 patients progressed to LF and were classified as the LF group, while the remaining 100 patients were classified as the non-LF (NLF) group. We compared the kinetic changes in clinical and immune indicators including age, total bilirubin level, prothrombin time, model for end-stage liver disease score, interleukin (IL)-6, IL-8, and IL-10 cytokine levels, and number of T helper 17 and regulatory T cells between groups to determine their association with progression to HBV-ACLF. The prognostic value of clinical and immune indicators was determined using the area under the receiver operating characteristic curve (AUC) value. Results: Cox regression analysis suggested that the plasma IL-6 level could predict CHB progression to HBV-ACLF (relative risk = 1.082, 95% confidence interval: 1.006-1.164; P=0.034). The AUC value, sensitivity, and specificity of baseline IL-6 level for predicting HBV-ACLF were 82.63%, 83.3%, and 82.9%, respectively (P=0.001). Conclusion: A high plasma IL-6 level in CHB patients could be an early biomarker for HBV-ACLF.

Activation of Nrf2 Pathway by Dimethyl Fumarate Attenuates Renal Ischemia-Reperfusion Injury.

BACKGROUND: Dimethyl fumarate (DMF) is a novel antioxidant that selectively reduces hydroxyl radicals. This study aimed to investigate the potential role of DMF in the pathogenesis of renal ischemia-reperfusion injury (IRI) and the mechanisms involved. METHODS: C57BL/6 wild-type mice were treated with DMF or a vehicle. Subsequently, renal IRI was induced in mice by a model of right kidney nephrectomy and left renal ischemia for 30 minutes followed by reperfusion for 24 hours. Sham operation and phosphate-buffered saline were used as controls. Serum and renal tissues were collected at 24 hours after IRI to evaluate the influence of DMF on the recovery of renal function after IRI. Blood urea nitrogen and serum creatinine levels were measured. Kidney cell apoptosis was evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling-positive staining. Interleukin 6 and tumor necrosis factor α cytokines in the kidney tissues were measured. Indicators of oxidative stress in the kidneys were detected. Finally, Nrf2-deficient mice were used to determine the protective role of the nuclear factor erythroid 2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1) signaling pathways induced by DMF using western blot assay. RESULTS: DMF significantly attenuated renal dysfunction in mice and showed reductions in the severity of renal tubular injury, cell necrosis, and apoptosis. Moreover, DMF significantly reduced the amount of key inflammatory mediators. Additionally, DMF attenuated the malondialdehyde levels 24 hours after IRI but upregulated the superoxide dismutase activities. Western blot assay showed that DMF significantly increased the protein levels of Nrf2, HO-1, and NQO-1. Importantly, these DMF-mediated beneficial effects were not observed in Nrf2-deficient mice. CONCLUSIONS: DMF attenuates renal IRI by reducing inflammation and upregulating the antioxidant capacity, which may be through Nrf2/HO-1and NQO1 signaling pathway.

Responsive hyaluronic acid-gold cluster hybrid nanogel theranostic systems.

Tumor microenvironment responsive and self-monitored multimodal synergistic theranostic strategies can significantly improve therapeutic efficacy by overcoming biological barriers. Herein, we report a type of smart fluorescent hyaluronic acid nanogel that can respond to the reducing microenvironment and activate tumor targeting with light-traceable monitoring in cancer therapy. First, the derivative of hyaluronic acid (HA) with a vinyl group and cystamine bisacrylamide were used to synthesize bioreducible HA based nanogels via copolymerization in aqueous medium. Then, multifunctional mHA-gold cluster (mHA-GC) hybrid nanogels were successfully prepared by the in situ reduction of gold salt in the HA nanogels. The HA matrix turns the nanogels into a capsule for effective drug loading with excellent colloidal stability. Interestingly, the reducing tumor microenvironment dramatically enhanced the fluorescence signal of gold clusters in the hybrid nanogels. The highly selective cancer cell uptake and efficient intratumoral accumulation of the hybrid nanogels were demonstrated by fluorescence tracking of these nanogels. Responsive disassembly of the hybrid nanogels and drug release were triggered by excess glutathione presence in cancer cells. Moreover, in vivo and in vitro tumor suppression assays revealed that the doxorubicin-loaded hybrid nanogels exhibited significantly superior tumor cell inhibition abilities compared to free DOX. Overall, the mHA-GC hybrid nanogels emerge as a promising theranostic nanoplatform for the targeted delivery and controlled release of antitumor drugs with light-traceable monitoring in cancer treatment.

Comprehensive analysis of long noncoding RNA and mRNA in five colorectal cancer tissues and five normal tissues.

The present study investigated the role of abnormally expressed mRNA and long noncoding RNA (lncRNA) in the development of colorectal cancer (CRC). We used lncRNA sequencing to analyze the transcriptome (mRNA and lncRNA) of five pairs of CRC tissues and adjacent normal tissues. The total expression of mRNAs and lncRNAs in each sample was determined using the R package and the gene expression was calculated using normalized FPKM. The structural features and expression of all detected lncRNAs were compared with those of mRNAs. Differentially expressed mRNAs were selected to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The functional analysis of differentially expressed lncRNAs was performed by analyzing the GO and KEGG enrichment of predicted cis-regulated target genes. A total of 18.2 × 108 reads were obtained by sequencing, in which the clean reads reached ≥ 94.67%, with a total of 245.2 G bases. The number of mRNAs and lncRNAs differentially expressed in CRC tissues and normal tissues were 113 and 6, respectively. Further predictive analysis of target genes of lncRNAs revealed that six lncRNA genes had potential cis-regulatory effects on 13 differentially expressed mRNA genes and co-expressed with 53 mRNAs. Up-regulated CTD-2256P15.4 and RP11-229P13.23 were the most important lncRNAs in these CRC tissues and involved in cell proliferation and pathway in cancer. In conclusion, our study provides evidence regarding the mRNA and lncRNA transcription in CRC tissues, as well as new insights into the lncRNAs and mRNAs involved in the development of CRC.

Polymer-based activatable optical probes for tumor fluorescence and photoacoustic imaging.

Optical imaging including fluorescence imaging and photoacoustic imaging have been widely employed in early and accurate diagnosis of cancer. Compared to the "always on" optical probes, the molecular probes that could emit their signal in response to the tumor microenvironment exhibit the low background noise and high signal-to-background ratio, allowing sensitive and accurate cancer diagnosis. Polymer-based activatable optical probes display the advantages of improved water solubility, good photostability, extended blood circulation time, and easy functionalization, which enable them to accumulate in tumor for early and accurate diagnosis. This review focuses on recent advances in the development of polymer-based activatable optical probes for tumor fluorescence and PA imaging. The designs of polymer-based optical probes are first discussed. Then the applications for tumor fluorescence and PA imaging using pH, hypoxia, reactive oxygen and nitrogen species, and enzymes responsive polymer-based optical probes are discussed in details. At last, the present challenges and perspectives of polymer-based activatable optical probes to further advance them into the clinical application are also suggested. This article is categorized under: Diagnostic Tools > In vivo Nanodiagnostics and Imaging Diagnostic Tools > Biosensing.

Targeting and microenvironment-improving of phenylboronic acid-decorated soy protein nanoparticles with different sizes to tumor.

It is essential for nanoparticles to delivery drugs accurately and penetrate deeply to tumor. However, complicated tumor microenvironment such as elevated tumor interstitial fluid pressure (IFP) and solid stress reduces the transport efficiency of nanomedicines in tumor. Methods: We herein report a drug delivery system of phenylboronic acid-decorated soy protein nanoparticles with the size of 30 nm, 50 nm and 150 nm. In vitro examinations including cytotoxicity, cellular uptake and penetration in multicellular tumor spheroids and in vivo observations including IFP and tumor solid stress measurements and antitumor activity were performed. Results: It was found that phenylboronic acid moiety could endow the nanoparticles actively targeting affinity to sialic acid (SA) which overexpressed in tumor cells. Simultaneously soy protein could improve tumor microenvironment such as reduction of IFP and tumor stress. Among the soy protein nanoparticles with different sizes, 30 nm-sized nanoparticles showed the best cellular uptake and highest cytotoxicity in vitro after loading doxorubicin (DOX). In vivo, 30 nm-sized nanoparticles showed the best tumor microenvironment improvement efficiency, leading to the enhanced drug accumulation and antitumor efficiency when combination with DOX. Conclusion: Our study introduces a bioactive nanoparticulate design strategy to actively target and significantly improve tumor microenvironment for enhanced cancer therapy.