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The keys to the prevention of tumor recurrence after operation are the elimination of residual tumor cells and the reversal of microenvironments that induce recurrence. In the formulation of a treatment scheme, building an appropriate drug delivery system is essential. An in-situ drug delivery system (ISDDS) is regarded as an effective treatment route for postoperative use that increases drug delivery efficiency and mitigates side-effects. ISDDS technology has been considerably improved through a clearer understanding of the mechanisms of postoperative recurrence and the development of drug delivery materials. This paper describes the initiation and characteristics of postoperative recurrence mechanisms. Based on this information, design principles for ISDDS are proposed, and a variety of practical drug delivery systems that fulfil specific therapeutic needs are presented. Challenges and future opportunities related to the application of in-situ drug carriers for inhibiting cancer recurrence are also discussed. Unlabelled Image • In-situ drug delivery system (ISDDS) is effective for postoperative drug delivery. • The mechanisms of microenvironment promoting tumor recurrence are summarized. • ISDDSs based on the mechanism of postoperative tumor recurrence • Perspectives of ISDDS for preventing postoperative tumor recurrence [ABSTRACT FROM AUTHOR]

Great attention has been paid to the impressive role the macromolecules played in cancer immunotherapy, however, the applications were largely limited by their poor circulation stability, low cellular uptake efficiency, and off-target effects. As an important messenger of intercellular communication, extracellular vesicles (EVs) exhibit unique advantages in macromolecule delivery compared to traditional synthetic carriers, offering new possibilities for modern drug delivery. These naturally derived carriers can achieve stable, efficient, and selective delivery of macromolecules and improve the efficacy and potentiality of macromolecular drugs in cancer immunotherapy. This review provides a brief overview of the unique features of EVs related to macromolecule delivery, the strategies and recent advances of using EVs as macromolecule delivery carriers in cancer immunotherapy. [Display omitted] • Advances in applying extracellular vesicles (EVs) for macromolecule delivery. • Uptake mechanism, pharmacokinetic characteristics, and biodistribution of EVs. • Perspectives of EV-based macromolecule delivery for cancer immunotherapy [ABSTRACT FROM AUTHOR]

Ferroptosis is an iron-dependent form of cell death accompanied by iron and lipid peroxidase accumulation and has drawn substantial attentions since its first discovery in 2012. Various studies have shown that tumor cells with high tumorigenicity, invasiveness, and metastatic potential are sensitive to ferroptosis. Consequently, many strategies to induce ferroptosis have been used in the design of antitumor nanodrug delivery systems (NDDSs). Prior reviews have thoroughly summarized the mechanism underlying ferroptosis, related pathways, and NDDSs materials. Recent studies have demonstrated that ferroptosis is interacted with several metabolic pathways, and these pathways have provided a basis for designing strategies for NDDSs-induced ferroptosis. Therefore, this review summarizes NDDSs designs for ferroptosis driven by different metabolic pathways, emphasizes the feasibility of inducing ferroptosis in cancer treatment, and finally discusses limitations of NDDSs and future developments in the field. [Display omitted] • Ferroptosis is involved in multiple metabolic pathway, such as iron, amino acids, lipid and mitochondria metabolism. • Working of different strategies to induce ferroptosis are discussed. • The application of nanodrug delivery systems (NDDSs) in ferroptosis-basic cancer therapy. [ABSTRACT FROM AUTHOR]

Tumor metastasis is a significant contributor to the mortality of cancer patients. Specifically, current conventional treatments are unable to achieve complete remission of brain metastasis. This is due to the unique pathological environment of brain metastasis, which differs significantly from peripheral metastasis. Brain metastasis is characterized by high tumor mutation rates and a complex microenvironment with immunosuppression. Additionally, the presence of blood-brain barrier (BBB)/blood tumor barrier (BTB) restricts drug leakage into the brain. Therefore, it is crucial to take account of the specific characteristics of brain metastasis when developing new therapeutic strategies. Nanomaterials offer promising opportunities for targeted therapies in treating brain metastasis. They can be tailored and customized based on specific pathological features and incorporate various treatment approaches, which makes them advantageous in advancing therapeutic strategies for brain metastasis. This review provides an overview of current clinical treatment options for patients with brain metastasis. It also explores the roles and changes that different cells within the complex microenvironment play during tumor spread. Furthermore, it highlights the use of nanomaterials in current brain treatment approaches. [Display omitted] • The unique pathological environment of brain metastases limits clinical outcomes. • Different cell types play different roles and change during the progression of BM. • NMs can be customized to specific pathological features and thus offer significant advantages in BM treatment. [ABSTRACT FROM AUTHOR]

Precisely reporting the inflammatory microenvironment, which can provide important basis for disease diagnosis and progression determination, is always challenging. In this work, we develop a targeting peptide-conjugated chemiluminescent reporter (OFF), which can be recognized by in-situ circulated neutrophils once injected, and then transported to the inflamed tissues characterized with overexpressed superoxide anion (O 2 −), assisted by the chemotaxis natural of neutrophils. Subsequently, the chemiluminescent probe can particularly respond to O 2 − to release the caged photons (ON) for visualizing inflammatory diseases such as subcutaneous tumor, colorectal cancer peritoneal metastasis (CCPM), ear swelling and kidney failure. The chemiluminescent probe provides a reliable tool to early detect inflammation and precisely excise micrometastatic lesions under optical guidance. This study provides a potential approach for improving the performance of luminophore in advanced bioimaging applications. [Display omitted] • An "off-to-on" chemiluminescent probe based on the structure of Schaap's dioxetanes is developed in this work • The probe transportation can inherit neutrophils' inherent inflammation-chemotaxis characteristic. • The probe can selectively respond to superoxide anion rich in inflammatory tissues. • The probe can specially and precisely image the foci of inflammatory disease. [ABSTRACT FROM AUTHOR]

Chelating Cu from tumors has been verified as an effective and promising strategy for cancer therapy through antiangiogenesis. However, systematic removal Cu by injecting with Cu chelators will result unavoidable side effects, since Cu is indispensable to the body. In this work, a micelle targeting to tumors' newborn vessels based on a polypeptide was developed to co-load DOX and Probe X, which can go through an "OFF-to-ON" procedure to report the Cu+-capture events in vivo in a real-time way by giving near infrared (NIR) fluorescence and photoacoustic signal. By co-delivering antiangiogenesis and chemotherapeutic reagents, the tumor can be significantly suppressed, meanwhile with a low systematic toxicity. Hopefully, this work can offer new insights in designing sophisticated antitumor strategy. Unlabelled Image • A theranostic specific Cu+ chelator was proposed. • Targeting micelle co-loaded with Cu+-chelator and chemotherapeutic reagents was fabricated. • Antiangiogenesis and tumor's oxygen saturation reduction were reduced. • Fine antitumor efficacy was achieved with low side effect. [ABSTRACT FROM AUTHOR]