Starvation therapy (ST), which aims to hinder the rapid proliferation of cancer cells by depriving oxygen and nutrients, has been considered an ideal approach for cancer treatment. However, the limitations of traditional ST schemes, such as low targeting efficacy, undesired systemic side effects, elevated tumor hypoxia, induced drug resistance, and increased tumor metastasis risk, limit clinical applications. To overcome these challenges, numerous nanomedicines have been engineered in recent years to advance ST-driven antitumor therapy. Against this backdrop, there is an urgent need to summarize the latest advances in advanced nanomaterial-enabled cancer starvation therapy. Herein, we aim to highlight the emerging breakthroughs at the intersection of ST, nanotechnology, and cancer treatment in this rapidly evolving field. This review focuses on several ST-related inducible strategies, including nutrient supply regulation, key nutrient deprivation, and some emerging approaches. Furthermore, it highlights the synergistic benefits of combining ST with other therapeutic modalities, including phototherapy, chemodynamic therapy, chemotherapy, ferroptosis, gas therapy, and immune therapy. Finally, the existing challenges and future perspectives on the clinical ST of tumors are discussed.

Ceratocystis fimbriata, a widespread plant pathogenic fungus, causes symptoms such as black spots, wilting, and death on various plants. Pomegranate wilt, caused by this fungus, is a devastating disease in which chlamydospores play a key role in the disease cycle. In this study, we performed transcriptomic and metabolic analyses on three C. fimbriata strains (A4, F1, and D1) obtained from the Plant Pathology Laboratory of Xichang University. We compared mycelia samples collected before and after chla-mydospore formation. Our analysis identified 3,395 differentially accumulated metab-olites and 4,268 differentially expressed genes. By integrating the transcriptome and metabolome data, we found 63, 44 and 57 metabolic pathways enriched in each strain, respectively. Notably, 29 pathways were shared across all three strains, predominantly those associated with amino acid biosynthesis, cofactor biosynthesis, carbon metabo-lism and 2-oxocarboxylic acid metabolism. Furthermore, genes related to branched-chain transaminase and citrate synthase-related genes were enriched in these core pathways. These findings suggest that branched-chain transaminase and citrate synthase play important roles in chlamydospore formation.

Ferroptosis has been widely explored as a promising cancer therapeutic target. Conventional ferroptosis induction relies on inhibiting glutathione peroxidase 4 (GPX4) to promote lipid peroxide accumulation. However, its efficacy is often limited by insufficient endogenous unsaturated lipids in tumor cells. To address this limitation, we developed a lipid-prodrug nanoamplifier (SIM-SS-LA NAs), composed of disulfide-linked linoleic alcohol and simvastatin (SIM) to enhance ferroptosis. Significant, the modularity of the prodrug not only promotes the assembly of the SIM but also amplifies its ferroptosis effect. In the highly reductive tumor microenvironment, disulfide bonds are cleaved, releasing SIM and LA. Notably, the released LA acts as an exogenous substrate, substantially increasing lipid peroxide accumulation and synergizing with SIM-mediated GPX4 inhibition to amplify ferroptosis. As expected, the lipid-prodrug nanoamplifier showed potent ferroptosis-driven antitumor activity in a 4T1 breast tumor-bearing mouse model, offering an efficient nanotherapeutic strategy for ferroptosis-based cancer therapy.

Oncolytic viruses (OVs) represent a promising cancer therapy due to their selective cytotoxicity, yet clinical success in lung cancer is hindered by biological barriers and immunosuppressive microenvironments. To address these barriers, an inhalable microbe-OVs consortium is developed by conjugating tumor-responsive PEGylated adenoviruses (Ads) to motile algae (Synechococcus WH8102) via click chemistry. Driven by algal motility, the consortium penetrates respiratory mucus and epithelial barriers to reach lung tumor sites. Intratumoral calcium ion deprivation by the algae disrupts cellular tight junctions and facilitates deep penetration into solid tumors, thereby potentiating Ads-mediated immunogenic cell death (ICD) and boosting microbial and viral co-activated antitumor immunity. Inhalation administration demonstrates robust antitumor effectiveness in murine lung tumor. This inhalable microbe-OV strategy provides a promising scheme for clinical oncolytic microorganism biotherapeutics.

Traditionally, intestinal bacteria have been regarded as risk factors for colorectal cancer (CRC). However, recent studies have gradually transformed them from “pathogenic risk” to “therapeutic strategies”. This transformation highlights their significant potential in the diagnosis and treatment of CRC. On one hand, specific intestinal bacteria contribute to the formation and progression of CRC. These bacteria not only serve as potential early diagnostic biomarkers but also enhance the efficacy of chemotherapy and immunotherapy by modulating the host immune response. On the other hand, certain specific intestinal bacteria possess the ability to directly kill tumor cells, exhibit tumor-targeting properties, and demonstrate excellent biocompatibility. Based on these characteristics, intestinal bacteria can also be engineered to serve as therapeutic agents or carriers for drug delivery, facilitating precise targeting and localized controlled release of therapeutic agents. To systematically review the cognitive shift from focusing on “pathogenic risk” to “therapeutic strategies”, this review summarized the therapeutic role of intestinal bacteria, specifically addressing four key aspects: diagnosis, adjuvant therapy, direct therapy, and carrier bionics. This may help to promote the development of innovative approaches for the diagnosis and treatment of CRC.

Chemotherapy is an important strategy in cancer treatment, and harnessing the immunomodulatory potential of chemotherapeutic agents presents novel opportunities for chemoimmunotherapy. The oxaliplatin (OXA) and gemcitabine (GEM) regimen, a clinically established protocol for solid tumors, primarily exerts therapeutic effects through synergistic cytotoxicity, with emerging evidence supporting its ancillary immune-modulating properties. However, intravenous administration is frequently associated with systemic toxicity and impedes precise control of drug ratios within the tumor. Furthermore, GEM undergoes rapid enzymatic degradation by cytidine deaminase (CDA), which is highly expressed in both tumor cells and intratumoral microbiota, compromising its efficacy and disrupting the therapeutic equilibrium with OXA. To overcome these limitations, we developed a sodium alginate (ALG)-based in situ hydrogel system for co-delivery of OXA, GEM, and the CDA inhibitor cedazuridine (CDZ) in a ratio-locked design. Following intratumoral injection, ALG underwent Ca2+-triggered gelation, facilitating localized drug retention and sustained synchronized release to mitigate off-target toxicity. CDZ enhanced the metabolic stability of GEM, maintaining the optimal GEM/OXA ratio. Concurrently, beyond cytotoxic synergy, OXA-triggered immunogenic cell death and GEM-driven regulatory T-cell depletion collectively enhance antitumor immunity. This ratio-locked localized delivery platform, integrated with metabolic stabilization, enables precise regimen control to achieve safe and potent chemoimmunotherapy.

The risk-benefit profile of mitoxantrone (MTO) in clinical settings is substantially limited by dose-limiting toxicities and a constrained therapeutic index. Human serum albumin (HSA) is an attractive carrier for chemotherapeutics, but its weak affinity for MTO hampers formulation stability and efficacy. To address this challenge, we developed an HSA-binding moiety engineering strategy by conjugating fatty alcohols (FAs, C8, C12, C16) to MTO through disulfide linkages, thereby introducing a high-affinity "molecular anchor" for HSA while ensuring tumor-selective drug release. These conjugates were formulated with HSA at varying mass ratios to optimize the nanoparticle assembly. Structure-activity analysis revealed that elongating FA chains significantly improved albumin affinity, nanoparticle stability, and therapeutic efficacy. The lead candidate, MTO-C16, exhibited optimal performance, forming stable HSA nanoparticles with enhanced pharmacokinetics, tumor accumulation, and antitumor potency. At an MTO-equivalent dose of 5 mg/kg, MTO-C16@HSA nanoparticles achieved robust tumor suppression with minimal off-target toxicity. This study introduces a versatile approach to enhance the therapeutic outcome of MTO and offers a broadly applicable platform for chemotherapeutics facing similar clinical challenges.

Albumin-based nanoparticle (ANP) drug delivery systems have achieved significant clinical success. However, the low affinity between Doxorubicin (DOX) and human serum albumin (HSA) hinders the formation of stable nanoparticles. In our studies, we initially conjugated DOX to disulfide bond-containing fatty alcohols via carboxamide bond to systematically evaluate the impact of carbon chain length (C4, C8, C12, C20) on the binding affinity between DOX and HSA. Notably, when the carbon chain length of fatty alcohols reached eight (C8), DOX exhibited strong binding affinity to HSA. However, these prodrugs exhibited weak cytotoxicity, indicating insufficient DOX release due to the stable carboxamide bond. To address this issue, we further replaced the stable carboxamide bond with relative active carbamate bond (DOX-OCO-C8). Under high glutathione (GSH) conditions in tumor cells, DOX-OCO-C8 ANPs exhibited accelerated hydrolytic activity and efficient release of DOX. The ANPs significantly improved the pharmacokinetic profile and antitumor efficacy of DOX while reducing systemic toxicity. Our findings suggested optimizing alkyl chain lengths and linker chemistry offers a promising strategy for developing effective and safe DOX prodrug ANPs.

Membrane-derived biomimetic nanovesicles have emerged as a promising platform in cancer immunotherapy due to their intrinsic biocompatibility, functional plasticity, and capability to modulate immune responses. By integrating various immunotherapeutic agents, including immune checkpoint inhibitors, tumor antigens, and immunostimulatory adjuvants, these vesicles can be engineered to mimic natural immune communication and overcome key barriers in the tumor immune microenvironment. This review summarizes recent advances in the design, functionalization, and application of biomimetic nanovesicles for anti-tumor immunity. We particularly highlight strategies that harness these vesicles to enhance innate and adaptive immune responses, reverse immune suppression, and synergize with existing immunotherapy modalities. Furthermore, we discuss the challenges associated with biosafety, large-scale manufacturing, and clinical translation. Continued innovation in vesicle engineering and immunological modulation will be crucial for transforming biomimetic nanovesicles into viable next-generation cancer immunotherapeutics.

Small-molecule prodrug nanoassemblies (SMP-NAs) represent a promising nanomedicine for cancer therapy, enabling carrier-free characteristics and facile fabrication. However, the development of SMP-NAs currently relies on empirical trial-and-error screening, as quantitative descriptors to predict the relationship between molecular structure and self-assembly remain unavailable. Here, we introduce chemical topology indices, traditionally restricted to small-molecule drug discovery, as predictive tools for the rational design of SMP-NAs. We synthesized three topological SN38 prodrugs with distinct topological architectures (linear, cyclic and branched) but identical lipophilicity. Topological indices quantitatively capture the critical molecular characteristics of the prodrugs. Notably, the branched architecture (SN38-Br) provides molecular flexibility for efficient core packing while maintaining sufficient steric hindrance to prevent over-aggregation. Consequently, SN38-Br NPs exhibited superior colloidal stability, systemic blood circulation, robust tumor accumulation and antitumor activity. Our work establishes a theoretical framework for the quantitative structure-activity relationship (QSAR) of SMP-NAs, offering a blueprint for the transition from empirical screening to Nano-QSAR.

Choroidoretinopathy is a major public health concern that causes significant vision impairment. Although therapeutic antibodies have demonstrated potential in treating these conditions, intravitreal injections remain invasive, associated with adverse effects, and require repeated traumatic administrations. Non-invasive drug delivery methods, such as eye drops, represent an ideal alternative but are limited by ocular barriers, making it difficult for drugs to effectively reach specific lesions. In this study, we introduce a novel reactive oxygen species (ROS)-responsive transmembrane peptide-antibody conjugate (PAC) designed for non-invasive, precise antibody delivery to the deep fundus region. The responsive PAC, termed trans-activator of transcription-polyethylene glycol-maleimide (TAT-MPEG)-antibody, is synthesized by linking transmembrane peptides TAT to maleimide via ROS-sensitive diselenide bonds, enabling efficient antibody conjugation. Following eye drop administration, TAT enhances ocular penetration, allowing the conjugate to traverse ocular barriers and deliver antibodies directly to the posterior segment. Moreover, the diselenide bonds facilitate antibody release in oxidative environments, ensuring targeted drug localization at disease sites. In mouse models of choroidal neovascularization and choroidal melanoma, this conjugate demonstrated significant therapeutic efficacy, highlighting its broad clinical potential for the treatment of choroidoretinopathy.

The clinical utility of doxorubicin (DOX) is significantly hampered by its non-selective cytotoxicity and the absence of desirable carriers. While human serum albumin (HSA) represents an excellent candidate for drug delivery, its application is often limited by a weak binding affinity for many therapeutic agents. Herein, a modular strategy was employed to construct HSA-based DOX prodrug nanoparticles (DOX-C14 &HSA NPs) to overcome these deficiencies. To improve tumor selectivity and the HSA-binding affinity of DOX, a pH-sensitive prodrug (DOX-C14) was first synthesized by conjugating DOX to myristic acid (C14) through a hydrazone linkage. Subsequently, through a simple sonication method and by regulating the optimal mass ratio of DOX-C14 to HSA at 1:1.5, we successfully produced DOX-C14 &HSA NPs that exhibited high stability, high encapsulation efficiency and significant drug loading. DOX-C14 &HSA NPs significantly improved the circulation time of DOX and efficiently released free DOX inside tumor cells, causing DNA damage and thus killing tumor cells. Consequently, this work not only overcomes the limitations of DOX but also introduces a new strategy applicable to other drugs for creating HSA-based nano-drugs, thereby broadening the potential of HSA in cancer therapy.

Overcoming the penetration barrier of nanomedicines remains a paramount challenge in antitumor therapy. Apoptotic bodies (ApoBDs), which are naturally generated from apoptotic cells, can mediate a potent neighboring effect by transferring drug to neighboring tumor cells via macropinocytosis. To amplify this process, we developed a tumor microenvironment-responsive nanoplatform (named as AD-NVs@CPP) to selectively enhance chemokine (C-X-C motif) receptor 4 (CXCR4) receptor-stimulated macropinocytosis. This platform was constructed by co-encapsulating doxorubicin (DOX) and the hypoxia-activated pro-drug AQ4N into homologous tumor cell membrane-derived nanovesicles (AD-NVs), followed by biomineralization of a calcium phosphate (CaP) shell that incorporated a CXCR4-targeting peptide (RFFE-SHAPAKPVSLSYR). The resultant AD-NVs@CPP exhibited a core-shell structure with a hydrodynamic diameter of similar to 180 nm and achieved a high peptide encapsulation efficiency of 81.6 % +/- 8.2 %. The CaP shell demonstrated excellent pH-responsive dissolution, releasing similar to 50 % of the peptide within 24 h at pH 6.5 ( vs. negligible release at pH 7.4), which consequently promoted cellular uptake and enhanced cytotoxicity under acidic conditions in vitro . Additionally, AD-NVs@CPP-induced ApoBDs served as efficient drug reservoirs, delivering drugs to adjacent cells with an IC50 value of 0.98 mu g/mL (in terms of protein concentration). In vivo , AD-NVs@CPP significantly prolonged the blood circulation time (increasing the halflife of DOX compared to the free drug solution) and improved tumor accumulation. Crucially, it enabled programmed drug penetration: AQ4N was selectively delivered into deep hypoxic tumor regions, mediating comprehensive tumor growth inhibition while maintaining a favorable safety profile. This work provides a robust strategy for achieving deep tumor penetration through the synergistic enhancement of macropinocytosis and the ApoBD-mediated neighboring effect. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Prodrug nanoassemblies formed by the self-assembly of prodrugs represent an emerging platform, offering advantages such as high drug loading, facile preparation, and tumor selectivity. However, existing prodrug nanoassemblies primarily depend on noncovalent intermolecular interactions to maintain structural integrity, rendering them vulnerable to in vivo instability and severely constraining their clinical translation. To overcome those limitations, we introduce a mild and efficient thiol-ene click reaction to construct prodrug nanoassemblies reinforced by a covalently crosslinked network. Specifically, prodrugs are designed by conjugating cabazitaxel (CTX) to tri-alkene-containing side chains via tumor redox-responsive bonds. These prodrugs spontaneously assemble into nanoassemblies enriched with surface-exposed olefin groups, which are subsequently "locked" by covalent crosslinking using tetra-arm thiol crosslinkers. The resulting covalently crosslinked prodrug nanoassemblies exhibit markedly improved stability, leading to prolonged systemic circulation and enhanced tumor accumulation, thereby translating into superior antitumor efficacy. Moreover, the redox-cleavable bond enables tumor microenvironment-responsive drug release, effectively mitigating the systemic toxicity of CTX while preserving its antitumor potency. Collectively, this covalent "locking" strategy provides a notable advancement in optimizing the structural stability of prodrug nanoassemblies and offers a promising strategy for developing novel chemotherapeutic delivery platforms that integrate circulatory stability with tumor selectivity.

Small interfering RNAs (siRNAs) have emerged as promising therapeutics for ulcerative colitis (UC) owing to their potent anti-inflammatory effects and favorable biocompatibility. However, effective oral siRNA delivery remains challenging due to limited inflammatory cell targeting, inefficient endosomal escape, and rapid degradation in the gastrointestinal tract. To overcome these barriers, we developed a nano-in-micro modular microbead system for colon-targeted delivery of siRNA against tumor necrosis factor-alpha (TNF-alpha). This platform integrates two key components: (i) a library of ginsenoside-based lipid nanoparticles (LNPs) generated by screening natural sterol analogues, among which ginsenoside Rg3-based LNPs (Rg3@siTNF-alpha) were identified as optimal carriers, enabling enhanced macrophage targeting via glucose transporter-1-mediated recognition and promoting endosomal escape by attenuating Niemann-Pick C1 (NPC1)-dependent recycling; and (ii) a calcium alginate (CA) shell that encapsulated Rg3@siTNF-alpha to form microbeads (CA@Rg3@siTNF-alpha), protecting the LNPs from premature degradation in the upper gastrointestinal tract. Upon colon-specific dissolution, CA@Rg3@siTNF-alpha released Rg3@siTNF-alpha, facilitating efficient macrophage uptake, rapid endosomal escape, and lipase-responsive siRNA release. Consequently, the microbeads alleviated UC by suppressing inflammation and oxidative stress, restoring epithelial barrier integrity, and rebalancing the gut microbiota. Collectively, this work presents a spatiotemporally controlled strategy for oral siRNA delivery with multi-mechanistic therapeutic actions.

The short half-life of local anesthetics often hinders postoperative pain (POP) management, as repeated or high-dose administration elicits risks of severe systemic toxicity and nerve fiber damage. While in-situ lyotropic liquid crystals (LLCs) hold promises as sustained-release depots, their clinical translation is severely paralyzed by extreme viscosity and reliance on irritating solvents, resulting in prohibitive injection resistance and severe tissue necrosis. To overcome these critical barriers, we developed a novel liquid crystal forming system (LCFS) driven by a strategic molecular design. By synergistically integrating diethylene glycol monoethyl ether (DGME) with a low-viscosity stabilizer lauric acid monoester with propane-1,2-diol (LAMP), we successfully decoupled sustained-release capability from high precursor viscosity. This structurally optimized LCFS exhibits exceptional needle passability before rapidly undergoing a water-triggered phase transition into highly ordered inverse hexagonal (HII) or cubic (Pn3m) nanostructures, creating a diffusion-regulating matrix. Notably, the HII and Pn3m nanostructures allow for compositional phase control to modulate release behavior, demonstrating prolonged in vitro release durations of over 7 days. In vivo evaluations demonstrated that a single injection of Bupivacaine-loaded LCFS delivered robust, continuous analgesia for an unprecedented 7 days in rigorous pain models. Crucially, this smart matrix maintained a flat, sub-toxic systemic pharmacokinetic profile, completely eradicating the lethal toxicity and extensive nerve demyelination characteristic of free drug equivalents. By resolving the critical injectability-biosafety paradox, this LCFS establishes a highly translatable, next-generation platform for ultra-long-acting POP management.

Prodrug nanoassemblies (NPs) have attracted much attention in improving the selectivity of chemotherapy drugs, while most of them suffer from poor targeting efficiency. Biotin, a well-known tumor-targeting ligand, can greatly enhance tumor accumulation. Herein, we construct the biotinylated prodrug (BiotinPTX) by connecting paclitaxel (PTX) to biotin via a disulfide bond, enabling the prodrug to self-assemble into nanoparticles (Biotin-PTX NPs). However, the pure NPs are observed to be rapidly cleared without polyethylene glycol (PEG) modifying, while excessive PEG can compromise their targeting efficiency, suggesting that it is crucial to optimize the amount of PEG. On this basis, the effect of distearoyl phosphatidylethanolamine-polyethylene glycol20 0 0 (DSPE-PEG2k ) ratios (0 %, 5 %, 10 %, 20 %, 40 % and 60 %, WPEG /Wprodrug + PEG ) on their performance have been investigated. The results provide evidence that BiotinPTX NPs containing 20 % DSPE-PEG2k (20 % NPs) can significantly improve colloidal stability and tumortargeting efficiency. Moreover, 20 % NPs exhibits good antitumor efficacy and safety compared with Taxol, Abraxane and Prodrug Sol. This work highlights the key role of moderate PEGylation in regulating the therapeutic performance of targeting NPs, offering a new way of thinking for tumor-targeting treatment. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Invasive pulmonary fungal diseases (IPFD) represent a growing global health crisis, with escalating incidence and mortality rates, posing a particularly life-threatening risk to immunocompromised populations. The complexity of diagnosis, limited therapeutic options, and the growing challenge of antifungal resistance have significantly constrained the clinical efficacy, leading to poor patient outcomes. Recently, the integration of revolutionary drug delivery platforms with classical antifungal agents, such as optimized nebulized amphotericin B, voriconazole-loaded liposomes and inhalable amphotericin B microspheres, has demonstrated significant clinical potential, particularly in pulmonary applications, by markedly enhancing biodistribution at the infection site while substantially minimizing systemic adverse effects. This comprehensive review synthesized recent advances in IPFD research, encompassing epidemiological characteristics, molecular pathogenesis, clinical manifestations, cutting-edge diagnostic technologies (including advanced imaging, fungal-specific biomarkers and molecular techniques like polymerase chain reaction (PCR) and next-generation sequencing) as well as formulation-based therapeutics that optimize pulmonary targeting to improve efficacy and reduce systemic toxicity. This review aimed to provide insights for the future development of precision-targeted delivery mechanisms and next-generation antifungal agents.

Nanodrug delivery systems show great potential in cancer therapy. However, conventional spherical nanoparticles are rapidly recognized and cleared by the mononuclear phagocyte system (MPS). This results in shortened circulation and inadequate tumor accumulation, which ultimately compromises the therapeutic efficacy. Previous studies have suggested that anisotropic morphologies, such as rod-like or worm-like nanostructures, can prolong blood circulation and promote tumor tissue-specific distribution. Nevertheless, controlling the morphology of nanoparticles without altering their chemical composition remains a significant challenge. In this study, we report a novel strategy for physical morphology regulation using prodrug nanoassemblies as a model. Specifically, this process refers to a noncovalent, energy-driven structural reorganization that proceeds without chemical bond cleavage or formation. An ultrasound-assisted one-step nanoprecipitation method is employed to controllably transform thioether-linked SN38 prodrugs (SN38-S-OA) from spherical nanoassemblies into highly uniform nanorods (NRs) with aspect ratios (AR) of 5 or 8. In contrast, the disulfide linkage provides more structural defects, which hinders similar structural reorganizations. Biological evaluations demonstrated that SN38-S-OA NRs AR5 achieved reduced macrophage uptake, prolonged blood circulation, enhanced tumor accumulation, and superior antitumor efficacy compared with those of SN38-S-OA NPs and SN38-SS-OA NPs. Additionally, an optimal aspect ratio is identified, as overly elongated SN38-S-OA NRs AR8 exhibited reduced tumor cell uptake due to increased steric hindrance. This study establishes purely physical morphology regulation as an independent design principle that prolongs circulation, enhances tumor targeting, and improves the therapeutic efficacy in nanomedicine.

The self-assembly prodrugs can be classified into hydrophobic and amphiphilic prodrugs. While hydrophobic prodrugs can form nanoassemblies through strong hydrophobic interactions, these tend to aggregate due to the high surface free energy. Amphiphilic prodrugs reduce surface energy but often lack a sufficient hydrophobic driving force for stable self-assembly. To overcome these limitations, we developed a prodrug coassembly strategy using a hydrophobic paclitaxel-palmitic acid (PA) prodrug (PTX-SS-PA) and three amphiphilic paclitaxel-oligoethylene glycol (OEG) prodrugs (PTX-SS-OEG1, PTX-SS-OEG4, and PTX-SS-OEG8). The results showed that coassembled nanoassemblies exhibit higher stability than self-assembled nanoassemblies. Furthermore, this study indicated that the cellular uptake efficiency, redox-sensitive activation efficiency, and cytotoxicity of coassembled nanoassemblies were affected by the OEG chain length. Notably, the OEG1@PA NPs exhibited the best tumor selectivity and redox-sensitive activation efficiency, resulting in potent antitumor activity and favorable safety. These findings present promising strategies for the development of advanced prodrug nanoassemblies.