Natural bioactive lysosomes extracted from multiple cells for tumor therapy.

Nanoparticles of biological origin exhibit many unique properties in biological applications due to their exquisite structure, specific composition, and natural biological functionality. In this study, we obtained lysosomes from three distinct cell types (one normal cell and two activated immune cells) and demonstrated their potential as natural therapeutic nanoparticles for tumor therapy. In vitro experiments revealed that these lysosomes maintained their structural integrity, were well-distributed, and exhibited significant biological activity, which effectively induced cancer cell death by generating ROS and disrupting biological substrates. Additionally, in vivo investigations showed that these lysosomes could accumulate in tumor tissues after intravenous administration and exhibited exceptional therapeutic effects through the destruction of tumor blood vessels and the degradation of immunosuppressive proteins, with complete tumor disappearance in a single treatment. This research on the utilization of bioactive lysosomes for tumor treatment provides valuable insights into drug development and tumor treatment, particularly when conventional approaches have proven ineffective.

Diurnal oscillations of epigenetic modifications are associated with variation in rhythmic expression of homoeologous genes in Brassica napus.

BACKGROUND: Epigenetic modifications that exhibit circadian oscillations also promote circadian oscillations of gene expression. Brassica napus is a heterozygous polyploid species that has undergone distant hybridization and genome doubling events and has a young and distinct species origin. Studies incorporating circadian rhythm analysis of epigenetic modifications can offer new insights into differences in diurnal oscillation behavior among subgenomes and the regulation of diverse expressions of homologous gene rhythms in biological clocks. RESULTS: In this study, we created a high-resolution and multioscillatory gene expression dataset, active histone modification (H3K4me3, H3K9ac), and RNAPII recruitment in Brassica napus. We also conducted the pioneering characterization of the diurnal rhythm of transcription and epigenetic modifications in an allopolyploid species. We compared the evolution of diurnal rhythms between subgenomes and observed that the Cn subgenome had higher diurnal oscillation activity in both transcription and active histone modifications than the An subgenome. Compared to the A subgenome in Brassica rapa, the An subgenome of Brassica napus displayed significant changes in diurnal oscillation characteristics of transcription. Homologous gene pairs exhibited a higher proportion of diurnal oscillation in transcription than subgenome-specific genes, attributed to higher chromatin accessibility and abundance of active epigenetic modification types. We found that the diurnal expression of homologous genes displayed diversity, and the redundancy of the circadian system resulted in extensive changes in the diurnal rhythm characteristics of clock genes after distant hybridization and genome duplication events. Epigenetic modifications influenced the differences in the diurnal rhythm of homologous gene expression, and the diurnal oscillation of homologous gene expression was affected by the combination of multiple histone modifications. CONCLUSIONS: Herein, we presented, for the first time, a characterization of the diurnal rhythm characteristics of gene expression and its epigenetic modifications in an allopolyploid species. Our discoveries shed light on the epigenetic factors responsible for the diurnal oscillation activity imbalance between subgenomes and homologous genes' rhythmic expression differences. The comprehensive time-series dataset we generated for gene expression and epigenetic modifications provides a valuable resource for future investigations into the regulatory mechanisms of protein-coding genes in Brassica napus.

Phenolic Profiles, Antihyperglycemic, Anti-Diabetic, and Antioxidant Properties of Egyptian Sonchus oleraceus Leaves Extract: An In Vivo Study.

This study aimed to investigate the phenolic and antioxidant properties of Egyptian Sonchus oleraceus leaves extract (SOE) while comparing the antihyperglycemic efficacy of SOE with that of conventional medicines (glibenclamide) in vivo as a substitution for insulin-deficient patients. Total phenolic (TPC) and flavonoid contents (TFC) in SOE contributed around 127.66 ± 0.56 mg GAE/gm as gallic acid equivalent (GAE) and 74.80 ± 0.55 mg QE/gm as quercetin equivalent (QE). SOE also showed significant DPPH scavenging activity at 43.46%. The presence of five phenolic and six flavonoid compounds in SOE was discovered by HPLC analysis. For the in vivo assay, 42 rats were distributed into six groups (7 Wister albino rats each). The standard control group was fed a basal diet. While the 35 rats were induced with a single dose of 100 mg kg-1 body weight (b.w.) alloxan, then treated orally with glibenclamide (GLI) at 10 mg kg-1, 100, 200, and 300 mg kg-1 SOE (positive control group) for 56 days of routine gastric oral gavages and compared to the effects of GLI, the treatment of SOE 200 and 300 mg kg-1 in diabetic rats for two months dramatically decreased blood glucose, total lipid, total cholesterol, and low-density lipoprotein cholesterol (LDLC) while boosting high-density lipoprotein cholesterol (HDLC) levels and improving liver and kidney functions. The histological assay revealed that the SOE 300 mg kg-1 treatment significantly improved the pancreas tissues, implying the potential application of Egyptian SOE as a diabetes treatment.

Elevating Second Near-Infrared Photothermal Conversion Efficiency of Hollow Gold Nanorod for a Precise Theranostic of Orthotopic Bladder Cancer.

The second near-infrared (NIR-II) window laser-activated agents have attracted broad interest in an orthotopic cancer theranostic. However, developing NIR-II photothermal agents (PTAs) with advanced photothermal conversion efficiency (PTCE) and tumor-specific response elevation remains a crucial challenge. Herein, a hollow gold nanorod (AuHNR) with a strong localized surface plasmon resonance (LSPR) peak in the NIR-II window was coated with MnO2 and chitosan to obtain AuHNR@MnO2@CS (termed AuMC) by a one-step method. Upon exposure to the tumor microenvironment (TME), the overexpressed GSH triggered degradation of the MnO2 layer to release Mn2+ and resulted in the PTCE elevation owing to exposure of the AuHNR. Consequently, photoacoustic and magnetic resonance imaging for accurate diagnosis, Mn2+-mediated chemodynamic therapy, and AuHNR elevating PT therapy for precise treatment could be achieved. Both in vitro and in vivo experiments confirmed the good performance of the AuMC on an orthotopic bladder cancer precise theranostic. This study provided NIR-II activated, TME-response PT conversion efficiency enhanced PTAs and offered a tumor-selective theranostic agent for orthotopic bladder cancer in clinical application.

Bio-evaluation of Untapped Alkaloids from Vinca minor Enriched by Methyl-jasmonate-induced Stress: an Integrated Approach.

The low amount of metabolites isolated from natural products is one of the challenges preventing their biological evaluation. The modulation of biosynthetic pathways by stimulating stress-induced responses in plants was proven to be a valuable tool for diversification of already known natural products. Recently, we reported the dramatic effect of methyl jasmonate (MeJA) on Vinca minor alkaloids distribution. In this study, three compounds identified as 9-methoxyvincamine, minovincinine, and minovincine are successfully isolated in good yield and subjected to several bioassays based on a network pharmacology study. The extracts and isolated compounds show weak to moderate antimicrobial and cytotoxic activities. Also, they are found to significantly promote wound healing in scratch assay, and transforming growth factor-ß (TGF-ß) modulation is suggested to be the potential pathway based on bioinformatic analysis. Hence, Western blotting is used to assess the expression of several markers related to this pathway and wound healing. The extracts and isolated compounds are able to increase the expression of Smad3 and Phosphatidylinositol-3-kinase (PI3K), while downregulating the levels of cyclin D1 and the mammalian target of rapamycin (mTOR) except for minovincine, which increases the mTOR expression, inferring that it might act through a different mechanism. Molecular docking is used to give insights on the ability of isolated compounds to bind with different active sites in mTOR. Collectively, the integrated phytochemical, in silico, and molecular biology approach reveal that V. minor and its metabolite could be repurposed for the management of dermatological disorders where these markers are dysregulated, which opens the gate to develop new therapeutics in the future.

Robust and facile label-free colorimetric aptasensor for ochratoxin A detection using aptamer-enhanced oxidase-like activity of MnO2 nanoflowers.

Ochratoxin A (OTA) is a powerful mycotoxin that can cause severe damage to human health, and its detection has attracted considerable attention in the field of food science. We present a robust and facile label-free colorimetric aptasensor for OTA detection using the aptamer-enhanced oxidase-like activity of MnO2 nanoflowers. The catalytic activities of the nanozymes could be improved by adsorption of the aptamers onto the MnO2 nanoflowers due to the increased affinity of the nanoflowers for the chromogenic substrate. The linear range for OTA detection varied from 0.05 to 33.35 ng/mL with a detection limit of 0.069 ng/mL. The limit of detection of the proposed strategy is equivalent to or even better than those of several previous methods. Moreover, the colorimetric aptasensor exhibited good specificity and stability for the analysis of OTA in wheat flour and red wine samples. Therefore, this method appears to have promising applications in the detection of mycotoxins.

Platelet-Covered Nanocarriers for Targeted Delivery of Hirudin to Eliminate Thrombotic Complication in Tumor Therapy.

Most patients are at high risk of thrombosis during cancer treatment. However, the major discrepancy in the therapeutic mechanisms and microenvironment between tumors and thrombosis makes it challenging for a panacea to treat cancer while being able to eliminate the risk of thrombosis. Herein, we developed a biomimetic MnOx/Ag2S nanoflower platform with platelet membrane modification (MnOx@Ag2S@hirudin@platelet membrane: MAHP) for the long-term release of anticoagulant drugs to treat thrombosis together with tumor therapy. This MAHP platform could achieve the targeted delivery of hirudin to the thrombus site and perform the controlled release under the irradiation of near-infrared light, demonstrating effective removal of the thrombus. Moreover, MAHP could inhibit tumor progression and prolong the survival time of mice with thromboembolic complications.

Polarization of Tumor-Associated Macrophages Promoted by Vitamin C-Loaded Liposomes for Cancer Immunotherapy.

While checkpoint blockade immunotherapy as a promising clinical modality has revolutionized cancer treatment, it is of benefit to only a subset of patients because of the tumor immunosuppressive microenvironment. Herein, we report that the specified delivery of vitamin C at the tumor site by responsive lipid nanoparticles can efficiently induce oxidative toxicity and the polarization of M1 macrophages, promoting the infiltration of activating cytotoxic T lymphocytes in the tumor microenvironment for intensive immune checkpoint blocking therapy. Both in vitro and in vivo assays demonstrate successful vitamin C-induced polarization of M2 macrophages to M1 macrophages. In vivo transcriptome analysis also reveals the activation mechanism of vitamin C immunity. More importantly, the combination approach displays much better immune response and immune process within the tumor microenvironment than clinical programmed cell death ligand 1 (Anti-PD-L1) alone. This work provides a powerful therapeutic application of vitamin C to amplify Anti-PD-L1 immunotherapy in cancer treatment, which brings hope to patients with clinically insensitive immunity.

Activation of TRPV1 by capsaicin-loaded CaCO3 nanoparticle for tumor-specific therapy.

Capsaicin is a natural non-toxic small molecular organic substance, which is often used clinically to reduce inflammation and pain. Here, we report an acid-responsive CaCO3 nanoparticle loaded with capsaicin that can specifically activate TRPV1 channels and trigger tumor calcium ion therapy. The excellent acid responsiveness of calcium carbonate enables it to precisely target the tumor sites. The released capsaicin can specifically activate TRPV1 channel, overloading the intracellular calcium ion concentration and causing cell apoptosis, which provides a new safer and cheaper treatment. We proved that the naturalness and non-toxicity of capsaicin make the CaCO3@CAP nanoparticles have excellent biocompatibility, which has good development prospects and clinical application potential.

Surgical Removal of Midurethral Sling in Women Undergoing Surgery for Presumed Mesh-Related Complications: A Systematic Review.

OBJECTIVE: To assess whether some, or all, of the mesh needs to be removed when a midurethral sling is removed for complications. DATA SOURCES: A systematic review and meta-analysis was conducted. MEDLINE, Cochrane, and ClinicalTrials.gov databases from January 1, 1996, through May 1, 2021, were searched for articles that met the eligibility criteria with total, partial, or a combination of anti-incontinence mesh removal. METHODS OF STUDY SELECTION: All study designs were included (N≥10), and a priori criteria were used for acceptance standards. Studies were extracted for demographics, operative outcomes, and adverse events. Meta-analysis was performed when possible. TABULATION, INTEGRATION, AND RESULTS: We double-screened 11,887 abstracts; 45 eligible and unique studies were identified. Thirty-five were single-group studies that evaluated partial mesh removal, five were single-group studies that evaluated total mesh removal, and five were studies that compared partial mesh removal with total mesh removal. All of the studies were retrospective in nature; there were no randomized controlled studies. Comparative studies demonstrated that partial mesh removal had lower rates of postoperative stress urinary incontinence (SUI) than total mesh removal (odds ratio 0.46, 95% CI 0.22-0.96). Single-group studies supported lower rates of postoperative SUI with partial mesh removal compared with total mesh removal (19.2% [95% CI 13.5-25.7] vs 48.7% [95% CI 31.2-66.4]). Both methods were similar with respect to associated pain, bladder outlet obstruction, mesh erosion or exposure, and lower urinary tract symptoms. Adverse events were infrequent. CONCLUSION: Postoperative SUI may be lower with partial mesh removal compared with total mesh removal. Other outcomes were similar regardless of the amount of mesh removed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD 42018093099.

Multifunctional Nanosystems with Enhanced Cellular Uptake for Tumor Therapy.

Rapid development of nanotechnology provides promising strategies in biomedicine, especially in tumor therapy. In particular, the cellular uptake of nanosystems is not only a basic premise to realize various biomedical applications, but also a fatal factor for determining the final therapeutic effect. Thus, a systematic and comprehensive summary is necessary to overview the recent research progress on the improvement of nanosystem cellular uptake for cancer treatment. According to the process of nanosystems entering the body, they can be classified into three categories. The first segment is to enhance the accumulation and permeation of nanosystems to tumor cells through extracellular microenvironment stimulation. The second segment is to improve cellular internalization from extracellular to intracellular via active targeting. The third segment is to enhance the intracellular retention of therapeutics by subcellular localization. The major factors in the delivery can be utilized to develop multifunctional nanosystems for strengthening the tumor therapy. Ultimately, the key challenges and prospective in the emerging research frontier are thoroughly outlined. This review is expected to provide inspiring ideas, promising strategies and potential pathways for developing advanced anticancer nanosystems in clinical practice.

Precise Chemodynamic Therapy of Cancer by Trifunctional Bacterium-Based Nanozymes.

Chemodynamic therapy (CDT) destroys cancer cells by converting H2O2 or O2 into reactive oxygen species (ROS), but its therapeutic efficacy is restricted by the antioxidant capacity of tumor. Previous solutions focused on strengthening the nanodrugs with the ability to increase ROS production or weaken the antioxidant capacity of cancer cells. Conversely, we here develop a mild nanodrug with negligible side effects. Specifically, the Au@Pt nanozyme decorated on a bacterial surface (Bac-Au@Pt) is reported to achieve precise CDT. Due to the tumor targeting ability of bacteria and catalytic property of Au@Pt nanozyme under acidic conditions, this nanosystem can release ROS to tumor cells effectively. In addition, the interferon gamma released by T cells specifically decreases the intracellular reductants in tumor cells, while having no obvious effect on normal cells. Therefore, a low dose of Bac-Au@Pt achieves a satisfactory therapeutic efficacy to tumor cells and is nontoxic to normal cells even at their acidic components. This nanosystem enables CDT and immunotherapy to mutually benefit and improve by each other, providing a promising strategy to achieve high anticancer efficacy even with a low dose usage.

Selective Thrombosis of Tumor for Enhanced Hypoxia-Activated Prodrug Therapy.

One of the main challenges for tumor vascular infarction in combating cancer lies in failing to produce sustained complete thrombosis. Inspired by the capability of vascular infarction in blocking the delivery of oxygen to aggravate tumor hypoxia, the performance of selective tumor thrombus inducing hypoxia activation therapy to improve the therapeutic index of coagulation-based tumor therapy is presented. By encapsulating coagulation-inducing protease thrombin and a hypoxia-activated prodrug (HAP) tirapazamine into metal-organic framework nanoparticles with a tumor-homing ligand, the obtained nanoplatform selectively activates platelet aggregation at the tumor to induce thrombosis and vascular obstruction therapy by the exposed thrombin. Meanwhile, the thrombus can cut off the blood oxygen supply and potentiate the hypoxia levels to enhance the HAP therapy. This strategy not only addresses the dissatisfaction of vascular therapy, but also conquers the dilemma of inadequate hypoxia in HAP treatment. Since clinical operations such as surgery can be used to induce coagulation, coagulation-based synergistic therapy is promising for translation into a clinical combination regimen.

Sexual function after pelvic organ prolapse surgery: a systematic review comparing different approaches to pelvic floor repair.

OBJECTIVE: Women consider preservation of sexual activity and improvement of sexual function as important goals after pelvic organ prolapse surgery. This systematic review aimed to compare sexual activity and function before and after prolapse surgery among specific approaches to pelvic organ prolapse surgery including native tissue repairs, transvaginal synthetic mesh, biologic grafts, and sacrocolpopexy. DATA SOURCES: MEDLINE, Embase, and ClinicalTrials.gov databases were searched from inception to March 2021. STUDY ELIGIBILITY CRITERIA: Prospective comparative cohort and randomized studies of pelvic organ prolapse surgeries were included that reported the following specific sexual function outcomes: baseline and postoperative sexual activity, dyspareunia, and validated sexual function questionnaire scores. Notably, the following 4 comparisons were made: transvaginal synthetic mesh vs native tissue repairs, sacrocolpopexy vs native tissue repairs, transvaginal synthetic mesh vs sacrocolpopexy, and biologic graft vs native tissue repairs. METHODS: Studies were double screened for inclusion and extracted for population characteristics, sexual function outcomes, and methodological quality. Evidence profiles were generated for each surgery comparison by grading quality of evidence for each outcome across studies using a modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Screening of 3651 abstracts was performed and identified 77 original studies. The overall quality of evidence was moderate to high. There were 26 studies comparing transvaginal synthetic mesh with native tissue repairs, 5 comparing sacrocolpopexy with native tissue repairs, 5 comparing transvaginal synthetic mesh with sacrocolpopexy, and 7 comparing biologic graft with native tissue repairs. For transvaginal synthetic mesh vs native tissue repairs, no statistical differences were found in baseline or postoperative sexual activity, baseline or postoperative total dyspareunia, persistent dyspareunia, and de novo dyspareunia. Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form change scores were not different between transvaginal synthetic mesh and native tissue repairs (net difference, -0.3; 95% confidence interval, -1.4 to 0.8). For sacrocolpopexy vs native tissue repairs, baseline or postoperative sexual activity, baseline or postoperative total dyspareunia, de novo dyspareunia, and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form score differences were not different. For biologic graft vs native tissue repairs, baseline or postoperative sexual activity, baseline or postoperative total dyspareunia, and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form changes were also not different. For transvaginal synthetic mesh vs sacrocolpopexy, there was no difference in sexual activity and sexual function score change. Based on 2 studies, postoperative total dyspareunia was more common in transvaginal synthetic mesh than sacrocolpopexy (27.5% vs 12.2%; odds ratio, 2.72; 95% confidence interval, 1.33-5.58). The prevalence of postoperative dyspareunia was lower than preoperative dyspareunia after all surgery types. CONCLUSION: Sexual function comparisons are most robust between transvaginal synthetic mesh and native tissue repairs and show similar prevalence of sexual activity, de novo dyspareunia, and sexual function scores. Total dyspareunia is higher after transvaginal synthetic mesh than sacrocolpopexy. Although sexual function data are sparse in the other comparisons, no other differences in sexual activity, dyspareunia, and sexual function score change were found.

Relationship of postoperative vaginal anatomy and sexual function: a systematic review with meta-analysis.

INTRODUCTION AND HYPOTHESIS: This was a planned secondary analysis of a systematic review that described sexual function outcomes following pelvic organ prolapse (POP) surgery. We aimed to describe the relationship of pre- and postoperative vaginal anatomic measures with sexual function outcomes. Data Sources included the Medline, Embase, and clinicaltrials.gov databases from inception to April 2018. METHODS: The original systematic review included prospective, comparative studies that reported sexual function outcomes before and following POP surgery. Studies were extracted for population characteristics, sexual function outcomes, and vaginal anatomy, including total vaginal length (TVL) and genital hiatus. By meta-regression, we analyzed associations across studies between vaginal anatomic measurements and sexual function using the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire-12 (PISQ-12) and dyspareunia outcomes. RESULTS: We screened 3124 abstracts and identified 74 papers representing 67 original studies. Among these, 14 studies reported TVL and PISQ-12 outcomes. Nine studies reported TVL and dyspareunia outcomes, eight studies reported GH and PISQ-12 outcomes, and seven studies reported GH and dyspareunia outcomes. We found no associations between anatomic measures and PISQ-12 or dyspareunia, although, we found a statistically significant association found between preoperative TVL and change in PISQ-12. CONCLUSION: Across studies, the evidence does not support an association between vaginal anatomy and either validated, condition-specific sexual function questionnaires or dyspareunia. However, no study has directly analyzed these associations in the setting of pelvic floor reconstructive surgery.

Bacteria Inspired Internal Standard SERS Substrate for Quantitative Detection.

Metal-respiring bacteria are frequently used to recycle metal resources by biosynthesizing nanoparticles on its surface in environment treatment. However, further utilization of biogenetic nanoparticles through combining the advantages of both bacteria and nanoparticles is still limited. Herein, biogenetic Au@Ag nanoislands are utilized as the surface-enhanced Raman spectroscopy (SERS) substrate for quantitative detection. Specifically, Au@Ag nanoislands enhance the Raman signal via surface plasmon resonance, while biomolecules (phospholipid, tyrosine, and phenylalanine, etc.) on bacterium serve as an internal standard to eliminate the discrepancy of the target SERS intensity in different hot spots. Gene-controlled biomolecules in bacteria guarantee the reproducibility of this SERS substrate. The generality of this analytical method is demonstrated by determining rhodamine 6G, malachite green, and uric acid. This discovery solves a pervasive problem in SERS analysis through a simple biogenetic nanosystem, which opens up an avenue to address scientific challenges by using versatile organisms from nature.

Changes in Sexual Activity and Function After Pelvic Organ Prolapse Surgery: A Systematic Review.

OBJECTIVE: We aimed to systematically review the literature to describe sexual activity and function before and after prolapse surgery. DATA SOURCES: We searched MEDLINE, EMBASE, and ClinicalTrials.gov databases from inception to April 2018. METHODS OF STUDY SELECTION: Prospective, comparative studies of reconstructive pelvic organ prolapse (POP) surgeries that reported sexual function outcomes were included. Studies were extracted for population characteristics, sexual function outcomes, and methodologic quality. Data collected included baseline and postoperative sexual activity, dyspareunia, and validated sexual function questionnaire scores. Change in validated scores were used to categorize overall sexual function as improved, unchanged, or worsened after surgery. TABULATION, INTEGRATION, AND RESULTS: The search revealed 3,124 abstracts and identified 74 articles representing 67 original studies. The overall quality of evidence was moderate to high. Studies reporting postoperative results found higher rates of sexual activity than studies reporting preoperative sexual activity in all POP surgeries except sacrospinous suspension, transvaginal mesh, and sacrocolpopexy. The prevalence of dyspareunia decreased after all prolapse surgery types. The risk of de novo dyspareunia ranged from 0% to 9% for all POP surgeries except posterior repair, which lacked sufficient data. Overall sexual function based on PISQ-12 (Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-12) scores improved for mixed native tissue repairs, anterior repairs, uterosacral suspensions, sacrospinous suspensions, and sacrocolpopexy; scores were similar for posterior repairs, transvaginal mesh, and biologic grafts. Sexual function did not worsen after any POP surgeries. CONCLUSION: Sexual function improves or remains unchanged after all types of reconstructive POP surgeries and does not worsen for any surgery type. Prevalence of total dyspareunia was lower after all POP surgery types, and de novo dyspareunia was low ranging 0-9%. This information can help surgeons counsel patients preoperatively. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019124308.

Ultrasmall Peptide-Coated Platinum Nanoparticles for Precise NIR-II Photothermal Therapy by Mitochondrial Targeting.

Photothermal therapy (PTT) is considered an alternative for oncotherapy because it has less invasive damage to normal tissues than other methods, particularly in second near-infrared (NIR-II) PTT (1000-1350 nm) because of deeper biological tissue penetration, lower photon scattering, and higher maximum permissible exposure (1.0 W cm-2). However, for achieving a higher therapeutic effect, the delivery of large amounts of NIR-sensitive agents has been pursued, which in turn enormously increases damage to normal cells. Herein, we developed peptide-coated platinum nanoparticles (TPP-Pt) to create violent damage for a given amount of hyperthermia by purposefully delivering TPP-Pt to the thermally susceptible mitochondria with minimal side effects. Mitochondrial peptide targeting endowed ultrasmall platinum nanoparticles (PtNPs) with monodispersity, high stability, biosafety, and enhanced uptake of cancer cells and priority of mitochondria, causing efficient PTT. Moreover, an in vivo experiment showed that the excellent tumor inhibitory effect and negligible side effects could be achieved with the preferentially striking thermosensitive mitochondria strategy. The mitochondria-based "win by one move" therapeutic platform of peptide-coated platinum nanoparticles (TPP-Pt) demonstrated here will find great potential to overcome the challenges of low therapeutic efficiency and strong systemic side effects in PTT.

Miniature Hollow Gold Nanorods with Enhanced Effect for In Vivo Photoacoustic Imaging in the NIR-II Window.

The miniaturization of gold nanorods exhibits a bright prospect for intravital photoacoustic imaging (PAI) and the hollow structure possesses a better plasmonic property. Herein, miniature hollow gold nanorods (M-AuHNRs) (≈46 nm in length) possessing strong plasmonic absorbance in the second near-infrared (NIR-II) window (1000-1350 nm) are developed, which are considered as the most suitable range for the intravital PAI. The as-prepared M-AuHNRs exhibit 3.5 times stronger photoacoustic signal intensity than the large hollow Au nanorods (≈105 nm in length) at 0.2 optical density under 1064 nm laser irradiation. The in vivo biodistribution measurement shows that the accumulation in tumor of miniature nanorods is twofold as high as that of the large counterpart. After modifying with a tumor-targeting molecule and fluorochrome, in living tumor-bearing mice, the M-AuHNRs group gives a high fluorescence intensity in tumors, which is 3.6-fold that of the large ones with the same functionalization. Moreover, in the intravital PAI of living tumor-bearing mice, the M-AuHNRs generate longer-lasting and stronger photoacoustic signal than the large counterpart in the NIR-II window. Overall, this study presents the fabrication of M-AuHNRs as a promising contrast agent for intravital PAI.

Biogenic Hybrid Nanosheets Activated Photothermal Therapy and Promoted Anti-PD-L1 Efficacy for Synergetic Antitumor Strategy.

Bacteria show promise for use in the field of combination cancer therapy because of their abilities to accumulate in tumors and their roles as natural immunologic adjuvants. However, the huge size of bacteria decreases their chances of being delivered into tumor cells. Moreover, their toxins may cause systemic toxicity in living organisms. Here, we proposed a method to in situ synthesize Au nanoparticles on the surface of Escherichia coli (E. coli), followed by sonication to acquire Au nanoparticles loaded membrane nanosheets (AuMNs) for use in photothermal and combination cancer therapy. Compared to E. coli-loaded Au nanoparticles (E. coli@Au), the small size of membrane nanosheets can be successfully delivered into tumor cells. In addition, the enrichment of AuMNs in tumor site is significantly enhanced via EPR effect, facilitating to activate photothermal conversion under 808 nm laser. Besides, the function of bacteria as natural immunologic adjuvants to promote anti-PD-L1 efficacy is still retained in AuMNs, while the inflammation and damage to viscera caused by AuMNs were milder than E. coli@Au. This study aims to decrease the systemic toxicity of bacteria and promote anti-PD-L1 efficacy in bacteria-mediated combination therapy, so as to open up a new avenue for drug delivery via natural processes.