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High recurrence rates after surgery and unacceptable side effects of chemotherapy and radiotherapy are challenges in the treatment of osteosarcoma (OS). Therefore, the development of nanoplatforms with combined tumor inhibition efficiency and fewer side effects is a promising strategy for the treatment of OS. In this paper, a biocompatible therapeutic nanoplatform (Fe-Zr@PDA@GOx) was constructed with a simple and efficient strategy for the treatment of OS. First, as an excellent Fenton reaction reagent, iron ions in the nanoplatform can generate highly toxic hydroxyl radicals (•OH) with hydrogen peroxide (H 2 O 2) in the tumor microenvironment and induce tumor cell death. Then, the modification of polydopamine endows the nanoplatform with photothermal responsiveness, with a photothermal conversion efficiency of 28.0%. Importantly, the conversed heat by polydopamine both promotes the release of glucose oxidase (GOx) and increases the rate of the Fenton reaction. Furthermore, GOx-mediated starvation treatment (SDT) can also provide suitable reaction conditions and sufficient H 2 O 2 to realize the amplification of chemodynamic therapy (CDT). Finally, the doping of Zr ions can interact with Fe to form dual active centers in the Fenton reaction and further accelerate the generation of •OH. Both in vitro and in vivo experiments reveal the synergistic photothermal/CDT/SDT anti-tumor effect. Therefore, this work provides an effective strategy for the treatment of OS. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Bi3+ induces the gelatinization of ALG and reacts with Na 2 S. • The Bi 2 S 3 NPs enable the CT imaging and the enhancement of tumor RT. • The sensitized RT enhances the hypoxia of TME and activates TPZ. • The Bi 2 S 3 NPs generate the hyperthermia to eradicate the cancer cells. Radiotherapy (RT) is becoming a pervasive therapeutic pattern in clinical cancer therapy. However, the hypoxic microenvironment of tumors has a strong resistance to radiotherapy and could lead to a potential recurrence and metastasis after the treatment. Therefore, the use of synergistic strategies for improving and supplementing the RT efficiency is important. Herein, a novel Bi 2 S 3 /alginate (ALG) hydrogel containing tirapazamine (TPZ) was designed for the effective suppression of tumor recurrence, by introducing Bi3+ into the ALG, Na 2 S and TPZ solution. In this formulation, Bi3+ was used to crosslink with the ALG to form the hydrogel and react with S2− to simultaneously form Bi 2 S 3 nanoparticles in the hydrogel matrix. The resulting Bi 2 S 3 nanoparticles not only exhibit the superb radiosensitization effect to boost the effective eradication of tumors during RT but also manifest an excellent photothermal transforming performance for tumor hyperthermia and computed tomography (CT) imaging capacity for tumor monitoring. Furthermore, the RT caused hypoxia could activate the reductive prodrug TPZ and enhance its therapeutic efficiency. The reported hydrogel system provides an efficient and safe therapeutic strategy for current local tumor therapy. [ABSTRACT FROM AUTHOR]

Some chemotherapy can damage tumor cells, releasing damage-related molecular patterns including ATP to improve immunological recognition against the tumor by immunogenic cell death (ICD). However, the immune-stimulating ATP may be rapidly degraded into immunosuppressive adenosine by highly expressed CD39 and CD73 in the tumor microenvironment, which leads to immune escape. Based on the above paradox, a liposome nanoplatform combined with ICD inducer (oxaliplatin) and CD39 inhibitor (POM-1) is designed for immunochemotherapy. The liposomes efficiently load the phospholipid-like oxaliplatin prodrug, and the cationic charged surface could adsorb POM-1. Rationally designed DSPE-PEG n -pep, on the one hand, could cover and hide POM-1 to avoid systematic toxicity and, on the other, achieve a response and charge reversal to favor POM-1 shedding and tumor deep penetration. This combination maximizes the ICD effect, and takes two-pronged advantage of stimulating the immune response and relieving immune suppression. The designed POL can effectively inhibit the growth of in situ, lung metastasis and postoperative recurrence melanoma model and form long-term immune memory. With the powerful clinical transformation potential of nanoliposome platforms, this new synergistic strategy is expected to enhance anticancer effects safely and effectively. [Display omitted] [ABSTRACT FROM AUTHOR]

Due to the pro-survival effect of mild autophagy, the therapeutic effect of chemo-immunotherapy is unsatisfactory. In addition, the adverse tumour microenvironment (TME), including the lack of antigen presentation, the deficiency of oxygen supply and immunosuppressive cells, results in immune escape and metastasis. Herein, a novel nanoplatform (CS–3BP/PA@DOX) based on the autophagy cascade is proposed for the first time to deliver the chemotherapeutic doxorubicin (DOX) and respiration inhibitor 3-bromopyruvic acid (3BP) to overcome the above obstacles. CS-3BP/PA@DOX exerts a synergistic therapeutic effect to initiate pro-death autophagy and facilitate the antigen presentation process by combining DOX chemotherapy and starvation therapy with 3BP. Additionally, CS-3BP/PA@DOX remodelled the immunosuppressive TME by alleviating hypoxia, damaging dense ECM, and downregulating PD-L1 to enhance antitumour immunity. 3BP was found to promote GSH depletion by inhibiting respiration for the first time, which reduces the chemical resistance of cancer and increases the sensitivity of cells to ROS, providing a new therapeutic direction of 3BP for antitumour treatment. Collectively, this study offers an opportunity to magnify pro-death autophagy, augment antitumour efficacy, facilitate anti-metastatic effects, and boost immune responses. [Display omitted] • CS-3BP/PA@DOX exerted a synergistic therapeutic effect to treat breast cancer. • This nanoplatform augmented anti-tumor efficacy and boosted immune responses. • CS-3BP/PA@DOX remodelled immunosuppressive tumor microenvironment. [ABSTRACT FROM AUTHOR]

• Tumor-specific deep penetration is realized by p-LDM. • Ferroptosis sensitization can be achieved by CA IX inhibition. • Self-amplified ferroptosis is realized by two structural components of p-LDM. • "p-LDM + anti-CD47" achieves enhanced therapeutic efficiency. As an approved chemotherapeutic drug for breast cancer (BC) therapy, the continuous application of doxorubicin (DOX) is unfortunately limited by its poor selectivity and the apoptosis resistance of tumor cells. To cope with the obstacles, this work developed a tumor-specific nanoplatform (named p-LDM) for DOX delivery and combinational ferroptosis-apoptosis activation. p-LDM was fabricated by coating ferric metal–organic framework (MOF) with liposomes and the outer liposomal membrane was further interspersed with targeting peptide-conjugated enzyme-activatiable cell-penetrating peptides (CPPs) to guarantee the tumor-specific penetration. As two components of the MOF core, Fe3+ (metal ion junction) triggered the ferroptosis of 4T1 cells via its self-cyclic valence alteration and terephthalic acid (H 2 BDC, organic ligand) reinforced the Fe3+-triggered ferroptosis by inhibiting carbonic anhydrase IX (CA IX); this self-amplifying strategy delicately boosted robust tumor ferroptosis. By combining DOX and ferroptosis activation, p-LDM performed forceful direct killing effect, immungentic cell death (ICD) stimulation, T cell activation and dendritic cell (DC) maturation promotion, suggesting its potential for synergetic apoptosis/ferroptosis activation and tumor immune microenvironment (TIM) remodeling. Further, p-LDM was combined with CD47-SIRPα blockade therapy, generating reinforced ferroptosis, which was largely attributed to the maximal up-regulation of IFN-γ levels and consequent system Xc- inhibition. Besides, the released "find me" signal from ferroptosis, "eat me" signal from ICD and the inhibited CD47-released "don't eat me" signal jointly remodeled the suppressive TIM, receiving superior synergistic inhibitions on tumor growth, metastasis and recurrence. [ABSTRACT FROM AUTHOR]