Long-Acting Nanohybrid Hydrogel Induces Persistent Immunogenic Chemotherapy for Suppressing Postoperative Tumor Recurrence and Metastasis.

Despite the continuous advancement of surgical resection techniques, postoperative tumor recurrence and metastasis remain a huge challenge. Here, we constructed an injectable curcumin/doxorubicin-loaded nanoparticle (NanoCD) hydrogel, which could effectively inhibit tumor regrowth and metastasis via reshaping the tumor immune microenvironment (TIME) for highly effective postsurgical cancer treatment. NanoCD was prepared by the controlled assembly of curcumin (CUR) and doxorubicin (DOX) via π-π stacking and hydrogen bonding in the presence of human serum albumin. To facilitate prolonged treatment of postsurgical tumors, NanoCD was further incorporated into the temperature-sensitive Poloxamer 407 gel (NanoCD@Gel) for intracavity administration. Mechanistically, DOX induced the generation of intracellular reactive oxygen species (ROS) and CUR reduced the ROS metabolism by inhibiting thioredoxin reductase (TrxR). The synergy of DOX and CUR amplified intracellular ROS levels and thus resulted in enhanced immunogenic cell death (ICD) of tumor cells. Upon being injected into the tumor cavity after resection, the in situ-generated NanoCD@Gel allowed the local release of CUR and DOX in a controlled manner to induce local chemotherapy and persistently activate the antitumor immune response, thereby achieving enhanced immunogenic chemotherapy with reduced systemic toxicity. Our work provides an elegant strategy for persistently stimulating effective antitumor immunity to prevent postsurgical tumor recurrence and metastasis.

Rationally Designed Monodisperse Gd2 O3 /Bi2 S3 Hybrid Nanodots for Efficient Cancer Theranostics.

Multifunctional nanotheranostic agents are of particular importance in the field of precise nanomedicine. However, a critical challenge remains in the rational fabrication of monodisperse multicomponent nanoparticles with enhanced multifunctional characteristics for efficient cancer theranostics. Here, a rational and facile synthesis of monodisperse Gd2 O3 /Bi2 S3 hybrid nanodots (Gd/Bi-NDs) is demonstrated as a multifunctional nanotheranostic agent using a albumin nanoreactor for computed tomography (CT)/photoacoustics (PA)/magnetic resonance (MR) imaging and simultaneous photothermal tumor ablation. Two nanoprecipitation reactions in one albumin nanoreactor are simultaneously conducted to generate ultrasmall Gd/Bi-NDs with both orthorhombic Bi2 S3 and cubic Gd2 O3 nanostructures. Their hybrid nanostructure generates distinctly enhanced longitudinal relaxivity in the spatially confined albumin nanocage as compared to monocomponent Gd2 O3 nanodots. Moreover, such hybrid nanodots possess multiple desirable characteristics including superior photobleaching resistance, efficient cellular uptake, preferable tumor accumulation, good in vivo clearance, and negligible acute toxicity, thereby leading to complementary PA/CT/MR imaging with spatial and anatomic characteristics, as well as effective photothermal tumor ablation without regrowth. These results represent a promising approach to fabricate monodisperse multicomponent nanotheranostic agents for efficient cancer theranostics.

Cyanine-Anchored Silica Nanochannels for Light-Driven Synergistic Thermo-Chemotherapy.

Smart nanoparticles are increasingly important in a variety of applications such as cancer therapy. However, it is still a major challenge to develop light-responsive nanoparticles that can maximize the potency of synergistic thermo-chemotherapy under light irradiation. Here, spatially confined cyanine-anchored silica nanochannels loaded with chemotherapeutic doxorubicin (CS-DOX-NCs) for light-driven synergistic cancer therapy are introduced. CS-DOX-NCs possess a J-type aggregation conformation of cyanine dye within the nanochannels and encapsulate doxorubicin through the π-π interaction with cyanine dye. Under near-infrared light irradiation, CS-DOX-NCs produce the enhanced photothermal conversion efficiency through the maximized nonradiative transition of J-type Cypate aggregates, trigger the light-driven drug release through the destabilization of temperature-sensitive π-π interaction, and generate the effective intracellular translocation of doxorubicin from the lysosomes to cytoplasma through reactive oxygen species-mediated lysosomal disruption, thereby causing the potent in vivo hyperthermia and intracellular trafficking of drug into cytoplasma at tumors. Moreover, CS-DOX-NCs possess good resistance to photobleaching and preferable tumor accumulation, facilitating severe photoinduced cell damage, and subsequent synergy between photothermal and chemotherapeutic therapy with tumor ablation. These findings provide new insights of light-driven nanoparticles for synergistic cancer therapy.

Cancer-Targeted Nanotheranostics: Recent Advances and Perspectives.

Cancer-targeted nanotechnology is experiencing the trend of finding new materials with multiple functions for imaging and therapeutic applications. With the rapid development of the related fields, there exists a large number of reports regarding theranostic nanomedicine, decreasing the gap between cancer diagnosis and treatment with minimized separate comprehensions. In order to present an overview on the cancer-targeted nanotheranostics, we first describe their essential building blocks, including platforms, therapeutic agents and imaging agents, and then the recently rapidly developed multimodal theranostic systems. Finally we discuss the major challenges and the perspectives of future development of nanotheranostics toward clinical translations and personalized nanomedicine.

Polyion complex vesicles for photoinduced intracellular delivery of amphiphilic photosensitizer.

Polymer vesicles formed by a pair of oppositely charged poly(ethylene glycol) (PEG)-based block aniomer and homocatiomer, termed "PICsomes", have tunable size, and are characterized by unique semipermeable property due to the flexible and tunable hydrophilicity of polyion complex (PIC) membranes. The PICsomes can encapsulate a variety of molecules in an inner aqueous phase just by a simple vortex mixing of solution, expecting their utility as nanocontainers of substances with biomedical interests. Here, we report on a new functionality of the PICsomes: photoinduced release of photoactive agents for intracellular drug delivery. A potent photosensitizer, Al(III) phthalocyanine chloride disulfonic acid (AlPcS2a), was efficiently incorporated into the PICsomes (11%(w/w)), and its quick release was induced by photoirradiation possibly due to the photochemical damage of the PIC membranes. The combination of a high-resolution fluorescent confocal microscopy and a lysosome membrane-specific staining method revealed that such photoinduced release of AlPcS2a occurred even in the lysosomes of living cells after endocytic internalization. Simultaneously, the released AlPcS2a photochemically affected the integrity of the lysosomal membranes, leading to the translocation of AlPcS2a and PICsomes themselves to the cytoplasm. Consequently, the AlPcS2a-encapsulated PICsomes (AlPcS2a-PICsomes) exhibited appreciably stronger photocytotoxicity compared with free AlPcS2a alone. Thus, the AlPcS2a-PICsomes have promising feasibility for the photodynamic therapy or the photoinduced cytoplasmic delivery of therapeutic molecules.

Causal associations between human gut microbiota and hemorrhoidal disease: A two-sample Mendelian randomization study.

Hemorrhoidal disease (HEM) is a common condition affecting a significant proportion of the population. However, the causal relationship between the gut microbiota and hemorrhoids remains unclear. In this study, we employed a Mendelian randomization (MR) approach to investigate the potential associations between them. In this study, the exposure factor was determined by selecting summary statistics data from a large-scale gut microbiome whole-genome association study conducted by the MiBioGen Consortium, which involved a sample size of 18,340 individuals. The disease outcome data consisted of 218,920 cases of HEM and 725,213 controls of European ancestry obtained from the European Bioinformatics Institute dataset. Two-sample MR analyses were performed to assess the causalities between gut microbiota and hemorrhoids using various methods, including inverse-variance weighting, MR-Egger regression, MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), simple mode, and weighted median. Reverse MR analyses were performed to examine reverse causal association. Our findings suggest phylum Cyanobacteria (OR = 0.947, 95% CI: 0.915-0.980, P = 2.10 × 10 - 3), genus Phascolarctobacterium (OR = 0.960, 95% CI: 0.924-0.997, P = .034) and family FamilyXI (OR = 0.974, 95% CI: 0.952-0.997, P = .027) have potentially protective causal effects on the risk of HEM, while genus Ruminococcaceae_UCG_002 (OR = 1.036, 95% CI: 1.001-1.071, P = .042), family Peptostreptococcaceae (OR = 1.042, 95% CI: 1.004-1.082, P = .029), genus Oscillospira (OR = 1.048, 95% CI: 1.005-1.091, P = .026), family Alcaligenaceae (OR = 1.048, 95% CI: 1.005-1.091, P = .036) and order Burkholderiales (OR = 1.074, 95% CI: 1.020-1.130, P = 6.50 × 10-3) have opposite effect. However, there was a reverse causal relationship between HEM and genus Oscillospira (OR = 1.140, 95% CI: 1.002-1.295, P = .046) This is the first MR study to explore the causalities between specific gut microbiota taxa and hemorrhoidal disease, which may offer valuable insights for future clinical interventions for hemorrhoidal disease.

Harness arsenic in medicine: current status of arsenicals and recent advances in drug delivery.

INTRODUCTION: Arsenicals have a special place in the history of human health, acting both as poison and medicine. Having been used to treat a variety of diseases in the past, the success of arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL) in the last century marked its use as a drug in modern medicine. To expand their role against cancer, there have been clinical uses of arsenicals worldwide and progress in the development of drug delivery for various malignancies, especially solid tumors. AREAS COVERED: In this review, conducted on Google Scholar [1977-2024], we start with various forms of arsenicals, highlighting the well-known ATO. The mechanism of action of arsenicals in cancer therapy is then overviewed. A summary of the research progress in developing new delivery approaches (e.g. polymers, inorganic frameworks, and biomacromolecules) in recent years is provided, addressing the challenges and opportunities in treating various malignant tumors. EXPERT OPINION: Reducing toxicity and enhancing therapeutic efficacy are guidelines for designing and developing new arsenicals and drug delivery systems. They have shown potential in the fight against cancer and emerging pathogens. New technologies and strategies can help us harness the potency of arsenicals and make better products.

A bioinspired doxorubicin-carried albumin Nanocage against aggressive Cancer via systemic targeting of tumor and lymph node metastasis.

Cancer metastasis and recurrence are obstacles to successful treatment of aggressive cancer. To address this challenge, chemotherapy is indispensable as an essential part of comprehensive cancer treatment, particularly for subsequent therapy after surgical resection. However, small-molecule drugs for chemotherapy always cause inadequate efficacy and severe side effects against cancer metastasis and recurrence caused by lymph node metastases. Here, we developed doxorubicin-carried albumin nanocages (Dox-AlbCages) with appropriate particle sizes and pH/enzyme-responsive drug release for tumor and lymph node dual-targeted therapy by exploiting the inborn transport properties of serum albumin. Inspired by the protein-templated biomineralization and remote loading of doxorubicin into liposomes, we demonstrated the controlled synthesis of Dox-AlbCages via the aggregation or crystallization of doxorubicin and ammonium sulfate within albumin nanocages using a biomineralization strategy. Dox-AlbCages allowed efficient encapsulation of Dox in the core protected by the albumin corona shell, exhibiting favorable properties for enhanced tumor and lymph node accumulation and preferable cellular uptake for tumor-specific chemotherapy. Intriguingly, Dox-AlbCages effectively inhibited tumor growth and metastasis in orthotopic 4T1 breast tumors and prevented postsurgical tumor recurrence and lung metastasis. At the same time, Dox-AlbCages had fewer side effects than free Dox. This nanoplatform provides a facile strategy for designing tumor- and lymph node-targeted nanomedicines for suppressing cancer metastasis and recurrence.

Nanoparticle-mediated TRPV1 channel blockade amplifies cancer thermo-immunotherapy via heat shock factor 1 modulation.

The survival of malignant tumors is highly dependent on their intrinsic self-defense pathways such as heat shock protein (HSP) during cancer therapy. However, precisely dismantling self-defenses to amplify antitumor potency remains unexplored. Herein, we demonstrate that nanoparticle-mediated transient receptor potential vanilloid member 1 (TRPV1) channel blockade potentiates thermo-immunotherapy via suppressing heat shock factor 1 (HSF1)-mediated dual self-defense pathways. TRPV1 blockade inhibits hyperthermia-induced calcium influx and subsequent nuclear translocation of HSF1, which selectively suppresses stressfully overexpressed HSP70 for enhancing thermotherapeutic efficacy against a variety of primary, metastatic and recurrent tumor models. Particularly, the suppression of HSF1 translocation further restrains the transforming growth factor ß (TGFß) pathway to degrade the tumor stroma, which improves the infiltration of antitumor therapeutics (e.g. anti-PD-L1 antibody) and immune cells into highly fibrotic and immunosuppressive pancreatic cancers. As a result, TRPV1 blockade retrieves thermo-immunotherapy with tumor-eradicable and immune memory effects. The nanoparticle-mediated TRPV1 blockade represents as an effective approach to dismantle self-defenses for potent cancer therapy.

A pH-Activatable Copper-Biomineralized Proenzyme for Synergistic Chemodynamic/Chemo-Immunotherapy against Aggressive Cancers.

Artificial enzymes have demonstrated therapeutic benefits against diverse malignant tumors, yet their antitumor potencies are still severely compromised by non-selective catalysis, low atomic-utilization efficiency, and undesired off-target toxicity. Herein, it is reported that peroxidase-like biomineralized copper (II) carbonate hydroxide nanocrystals inside single albumin nanocages (CuCH-NCs) act as a pH-activatable proenzyme to achieve tumor-selective and synergistic chemodynamic/chemo-immunotherapy against aggressive triple-negative breast cancers (TNBCs). These CuCH-NCs show pH-sensitive Cu2+ release, which spontaneously undergoes glutathione (GSH)-mediated reduction into Cu+ species for catalyzing the evolution of H2 O2 into hydroxyl radicals (·OH) in a single-atom-like manner to cause chemodynamic cell injury, and simultaneously activates non-toxic disulfiram to cytotoxic complex for yielding selective chemotherapeutic damage via blocking cell proliferation and amplifying cell apoptosis. CuCH-NCs exhibit considerable tumor-targeting capacity with deep penetration depth, thus affording preferable efficacy against orthotopic breast tumors through synergistic chemodynamic/chemotherapy, together with good in vivo safety. Moreover, CuCH-NCs arouse distinct immunogenic cell death effect and upregulate PD-L1 expression upon disulfiram combination, and thus synergize with anti-PD-L1 antibody to activate adaptive and innate immunities, together with relieving immunosuppression, finally yielding potent antitumor efficacy against both primary and metastatic TNBCs. These results provide insights into smart and high-performance proenzymes for synergistic therapy against aggressive cancers.

Holographically Activatable Nanoprobe via Glutathione/Albumin-Mediated Exponential Signal Amplification for High-Contrast Tumor Imaging.

Glutathione (GSH)-activatable probes hold great promise for in vivo cancer imaging, but are restricted by their dependence on non-selective intracellular GSH enrichment and uncontrollable background noise. Here, a holographically activatable nanoprobe caging manganese tetraoxide is shown for tumor-selective contrast enhancement in magnetic resonance imaging (MRI) through cooperative GSH/albumin-mediated cascade signal amplification in tumors and rapid elimination in normal tissues. Once targeting tumors, the endocytosed nanoprobe effectively senses the lysosomal microenvironment to undergo instantaneous decomposition into Mn2+ with threshold GSH concentration of ≈ 0.12 mm for brightening MRI signals, thus achieving high contrast tumor imaging and flexible monitoring of GSH-relevant cisplatin resistance during chemotherapy. Upon efficient up-regulation of extracellular GSH in tumor via exogenous injection, the relaxivity-silent interstitial nanoprobe remarkably evolves into Mn2+ that are further captured/retained and re-activated into ultrahigh-relaxivity-capable complex by stromal albumin in the tumor, and simultaneously allows the renal clearance of off-targeted nanoprobe in the form of Mn2+ via lymphatic vessels for suppressing background noise to distinguish tiny liver metastasis. These findings demonstrate the concept of holographic tumor activation via both tumor GSH/albumin-mediated cascade signal amplification and simultaneous background suppression for precise tumor malignancy detection, surveillance, and surgical guidance.

Smart drug delivery systems for precise cancer therapy.

Nano-drug delivery strategies have been highlighted in cancer treatment, and much effort has been made in the optimization of bioavailability, biocompatibility, pharmacokinetics profiles, and in vivo distributions of anticancer nano-drug delivery systems. However, problems still exist in the delicate balance between improved anticancer efficacy and reduced toxicity to normal tissues, and opportunities arise along with the development of smart stimuli-responsive delivery strategies. By on-demand responsiveness towards exogenous or endogenous stimulus, these smart delivery systems hold promise for advanced tumor-specificity as well as controllable release behavior in a spatial-temporal manner. Meanwhile, the blossom of nanotechnology, material sciences, and biomedical sciences has shed light on the diverse modern drug delivery systems with smart characteristics, versatile functions, and modification possibilities. This review summarizes the current progress in various strategies for smart drug delivery systems against malignancies and introduces the representative endogenous and exogenous stimuli-responsive smart delivery systems. It may provide references for researchers in the fields of drug delivery, biomaterials, and nanotechnology.

Self-activated arsenic manganite nanohybrids for visible and synergistic thermo/immuno-arsenotherapy.

Arsenotherapy has been clinically exploited to treat a few types of solid tumors despite of acute promyelocytic leukemia using arsenic trioxide (ATO), however, its efficacy is hampered by inadequate delivery of ATO into solid tumors owing to the absence of efficient and biodegradable vehicles. Precise spatiotemporal control of subcellular ATO delivery for potent arsenotherapy thus remains challengeable. Herein, we report the self-activated arsenic manganite nanohybrids for high-contrast magnetic resonance imaging (MRI) and arsenotherapeutic synergy on triple-negative breast cancer (TNBC). The nanohybrids, composed of arsenic­manganese-co-biomineralized nanoparticles inside albumin nanocages (As/Mn-NHs), switch signal-silent background to high proton relaxivity, and simultaneously afford remarkable subcellular ATO level in acidic and glutathione environments, together with reduced ATO resistance against tumor cells. Then, the nanohybrids enable in vivo high-contrast T1-weighted MRI signals in various tumor models for delineating tumor boundary, and simultaneously yield efficient arsenotherapeutic efficacy through multiple apoptotic pathways for potently suppressing subcutaneous and orthotopic breast models. As/Mn-NHs exhibited the maximum tumor-to-normal tissue (T/N) contrast ratio of 205% and tumor growth inhibition rate of 88% at subcutaneous 4T1 tumors. These nanohybrids further yield preferable synergistic antitumor efficacy against both primary and metastatic breast tumors upon combination with concurrent thermotherapy. More importantly, As/Mn-NHs considerably induce immunogenic cell death (ICD) effect to activate the immunogenically "cold" tumor microenvironment into "hot" one, thus synergizing with immune checkpoint blockade to yield the strongest tumor inhibition and negligible metastatic foci in the lung. Our study offers the insight into clinically potential arsenotherapeutic nanomedicine for potent therapy against solid tumors.

Correlation between serum miR-122 and myocardial damage and ventricular function in patients with essential hypertension.

BACKGROUND: Myocardial damage and decreased ventricular function are risk factors leading to a bad prognosis in patients with essential hypertension (EH). MicroRNAs play important roles in myocardial function impairment in patients with hypertension. The purpose of our research was to investigate the correlation between serum miR-122 and myocardial damage and ventricular functions in EH patients. METHODS: The clinic data of EH patients (group A, n=60) and healthy individuals (group B, n=60) from December 2016 to December 2019 in our hospital were collected and analyzed. Serum miR-122, myocardial damage markers [B-type brain natriuretic peptide (BNP), homocysteine (Hcy), cardiac troponin T (cTnT) and creatine kinase MB isoenzyme (CK-MB)] and cardiac function indicators [ejection fraction (EF), left ventricular septal thickness (IVST), left ventricular isovolumic relaxation time (IVRT), left ventricular end-diastolic diameter (LVEDD), left ventricular posterior wall thickness (LVPWT), and left ventricular end-systolic diameter (LVESD)] were assessed in both groups. The correlation between serum miR-122 and myocardial damage markers and ventricular function indicators was analyzed. RESULTS: (I) The mean serum miR-122 concentration in group A and group B was 6.86±1.23 and 3.36±1.87 µmol/L, respectively. The serum miR-122 concentration in group A was evidently increased compared with that in group B. (II) The levels of BNP, Hcy, cTnT, and CK-MB in the peripheral blood in group A were evidently increased compared with those in group B (P<0.05). (III) EF and IVRT were evidently decreased in group A compared with that in group B (P<0.05). (IV) Serum miR-122 concentration was positively correlated with the myocardial damage markers BNP, Hcy, cTnT and CK-MB, and serum miR-122 concentration was negatively correlated with the ventricular function indicators EF and IVRT but not significantly correlated with other ventricular function indicators (IVST, LVEDD, LVPWT and LVESD). CONCLUSIONS: The serum miR-122 concentration in EH patients was higher than that in healthy individuals, and miR-122 concentration was positively correlated with myocardial damage markers. Serum miR-122 level was negatively correlated with the ventricular function indicators EF and IVRT but was not significantly correlated with other ventricular function indicators (IVST, LVEDD, LVPWT, and LVESD).

Highly Efficient Far-Red/NIR-Absorbing Neutral Ir(III) Complex Micelles for Potent Photodynamic/Photothermal Therapy.

A critical issue in photodynamic therapy (PDT) is inadequate reactive oxygen species (ROS) generation in tumors, causing inevitable survival of tumor cells that usually results in tumor recurrence and metastasis. Existing photosensitizers frequently suffer from relatively low light-to-ROS conversion efficiency with far-red/near-infrared (NIR) light excitation due to low-lying excited states that lead to rapid non-radiative decays. Here, a neutral Ir(III) complex bearing distyryl boron dipyrromethene (BODIPY-Ir) is reported to efficiently produce both ROS and hyperthermia upon far-red light activation for potentiating in vivo tumor suppression through micellization of BODIPY-Ir to form "Micelle-Ir". BODIPY-Ir absorbs strongly at 550-750 nm with a band maximum at 685 nm, and possesses a long-lived triplet excited state with sufficient non-radiative decays. Upon micellization, BODIPY-Ir forms J-type aggregates within Micelle-Ir, which boosts both singlet oxygen generation and the photothermal effect through the high molar extinction coefficient and amplification of light-to-ROS/heat conversion, causing severe cell apoptosis. Bifunctional Micelle-Ir that accumulates in tumors completely destroys orthotopic 4T1 breast tumors via synergistic PDT/photothermal therapy (PTT) damage under light irradiation, and enables remarkable suppression of metastatic nodules in the lungs, together without significant dark cytotoxicity. The present study offers an emerging approach to develop far-red/NIR photosensitizers toward potent cancer therapy.

Immune Checkpoint Inhibitor-Based Strategies for Synergistic Cancer Therapy.

Immune checkpoint blockade therapy (ICBT) targeting checkpoints, such as, cytotoxic T-lymphocyte associated protein-4 (CTLA-4), programmed death-1 (PD-1), or programmed death-ligand 1 (PD-L1), can yield durable immune response in various types of cancers and has gained constantly increasing research interests in recent years. However, the efficacy of ICBT alone is limited by low response rate and immune-related side effects. Emerging preclinical and clinical studies reveal that chemotherapy, radiotherapy, phototherapy, or other immunotherapies can reprogramm immunologically "cold" tumor microenvironment into a "hot" one, thus synergizing with ICBT. In this review, the working principle and current development of various immune checkpoint inhibitors are summarized, while the interactive mechanism and recent progress of ICBT-based synergistic therapies with other immunotherapy, chemotherapy, phototherapy, and radiotherapy in fundamental and clinical studies in the past 5 years are depicted and highlighted. Moreover, the potential issues in current studies of ICBT-based synergistic therapies and future perspectives are also discussed.

Biomineralized iron oxide-polydopamine hybrid nanodots for contrast-enhanced T1-weighted magnetic resonance imaging and photothermal tumor ablation.

Iron oxide nanoparticles (IO NPs) have become the focus of molecular imaging probes for contrast enhanced magnetic resonance (MR) imaging due to their intrinsic magnetic and biodegradable properties, as well as long blood half-lives and low toxicity. Massive efforts have been made to explore the IO NPs as T2-weighted MR contrast agents, which have high susceptibility to induce a long-range magnetic field that interferes with diagnosis. Thus, the development of IO NPs with potent T1 relaxivity might help in providing an alternative for clinically applied gadolinium chelates. Herein, biomineralized iron oxide-polydopamine hybrid nanodots (IO/PDA-NDs) have been constructed using albumin as the nanoreactors to induce nanoprecipitation and polymerization simultaneously, facilitating T1-weighted contrast-enhancement as well as photothermal therapeutic capability. The IO nanoclusters in IO/PDA-NDs have an r1 relaxivity of 5.79 mM-1 s-1 with a relatively low r2/r1 ratio of 1.71, demonstrating the preferable iron oxide based T1 contrast agents. The high photothermal conversion coefficient and tumor targeting effect of the hybrid nanodots could result in complete tumor ablation efficacy. The biomineralization method provides a promising approach for the integration of tumor diagnosis and treatment to achieve efficient cancer theranostics.

Serum protein-based nanoparticles for cancer diagnosis and treatment.

Serum protein as naturally essential biomacromolecules has recently emerged as a versatile carrier for diagnostic and therapeutic drug delivery for cancer nanomedicine with superior biocompatibility, improved pharmacokinetics and enhanced targeting capacity. A variety of serum proteins have been utilized for drug delivery, mainly including albumin, ferritin/apoferritin, transferrin, low-density lipoprotein, high-density lipoprotein and hemoglobin. As evidenced by the success of paclitaxel-bound albumin nanoparticles (AbraxaneTM), serum protein-based nanoparticles have gained attractive attentions for precise biological design and potential clinical application. In this review, we summarize the general design strategies, targeting mechanisms and recent development of serum protein-based nanoparticles in the field of cancer nanomedicine. Moreover, we also concisely specify the current challenges to be addressed for a bright future of serum protein-based nanomedicines.

Heavy-Atom-Modulated Supramolecular Assembly Increases Antitumor Potency against Malignant Breast Tumors via Tunable Cooperativity.

Triple-negative breast cancer (TNBC) remains with highest incidence and mortality rates among females, and a critical bottleneck lies in rationally establishing potent therapeutics against TNBC. Here, the self-assembled micellar nanoarchitecture of heavy-atom-modulated supramolecules with efficient cytoplasmic translocation and tunable photoconversion is shown, for potent suppression against primary, metastatic, and recurrent TNBC. Multi-iodinated boron dipyrromethene micelles yield tunable photoconversion into singlet oxygen and a thermal effect, together with deep penetration and subsequent cytoplasmic translocation at the tumor. Tetra-iodinated boron dipyrromethene micelles (4-IBMs) particularly show a distinctly enhanced cooperativity of antitumor efficiency through considerable expressions of apoptotic proteins, potently suppressing subcutaneous, and orthotopic TNBC models, together with reduced oxygen dependence. Furthermore, 4-IBMs yield preferable anti-metastatic and anti-recurrent efficacies through the inhibition of metastasis-relevant proteins, distinct immunogenic cell death, and re-education of M2 macrophages into tumoricidal M1 phenotype as compared to chemotherapy and surgical resection. These results offer insights into the cooperativity of supramolecular nanoarchitectures for potent phototherapy against TNBC.

Immunotherapy and Prevention of Cancer by Nanovaccines Loaded with Whole-Cell Components of Tumor Tissues or Cells.

Tumor tissues/cells are the best sources of antigens to prepare cancer vaccines. However, due to the difficulty of solubilization and delivery of water-insoluble antigens in tumor tissues/cells, including water-insoluble antigens into cancer vaccines and delivering such vaccines efficiently to antigen-presenting cells (APCs) remain challenging. To solve these problems, herein, water-insoluble components of tumor tissues/cells are solubilized by 8 m urea and thus whole components of micrometer-sized tumor cells are reasssembled into nanosized nanovaccines. To induce maximized immunization efficacy, various antigens are loaded both inside and on the surface of nanovaccines. By encapsulating both water-insoluble and water-soluble components of tumor tissues/cells into nanovaccines, the nanovaccines are efficiently phagocytosed by APCs and showed better therapeutic efficacy than the nanovaccine loaded with only water-soluble components in melanoma and breast cancer. Anti-PD-1 antibody and metformin can improve the efficacy of nanovaccines. In addition, the nanovaccines can prevent lung cancer (100%) and melanoma (70%) efficiently in mice. T cell analysis and tumor microenvironment analysis indicate that tumor-specific T cells are induced by nanovaccines and both adaptive and innate immune responses against cancer cells are activated by nanovaccines. Overall, this study demonstrates a universal method to make tumor-cell-based nanovaccines for cancer immunotherapy and prevention.