Efficient Cancer Therapy Research Articles

In Vitro and In Vivo Evaluation of the Effectiveness and Safety of Amygdalin as a Cancer Therapy.

Cancer is one of the most important causes of death worldwide. Several studies have shown the efficacy of apricot kernel seed as a cancer therapy due to the presence of amygdalin. These studies have demonstrated amygdalin's cytotoxicity, antioxidant activity, and apoptosis in vitro using human cancer cell lines. However, no studies have demonstrated their cancer activity in vivo. The aim of this study is to develop an amygdalin-loaded niosomes (ALN) gel formulation as a drug delivery system in order to investigate the selectivity, efficacy, and toxicity of amygdalin as a cancer therapy in vivo using the 7,12-dimethylbenz (a) anthracene (DMBA) carcinoma rat model. Based on pre-formulation studies, the ALN formulation composed of Tween 60: cholesterol: dihexadecyl phosphate in a molar ratio of 1:2:0.1 was chosen as an optimum formulation because it has a percent of EE of 66.52% with a particle size of 269.3 nm and a reflux of 3.54 µg.cm-2.h-1. The ALN gel formulation was integrated into carbopol gel to be evaluated in vivo. Compared to DMBA control, treatment with ALN gel showed a reduction in the carcinoma volume and in the hyperplasia of the epidermis with no signs of edema. In conclusion, the ALN gel formulation could be an efficient cancer therapy.

WITHDRAWN: Poly(caprolactone)-b-Poly(ethylene glycol)-based Polymeric Micelles as Drug Carrier for Efficient Breast Cancer Therapy: A Systematic Review

Recently, drug delivery systems based on nanoparticles for cancer treatment have become the centre of attention for researchers to design and fabricate drug carriers for anticancer drugs due to the conventional pharmaceuticals lacking tumour-targeting activity. Poly(caprolactone)- b -poly(ethylene glycol) (PCL-PEG)-based micelles have attracted significant attention as a potential drug carrier intended for human use. Since their first discovery, the Food and Drug Administration (FDA)-approved polymers have been studied extensively for various biomedical applications, specifically cancer therapy. The application of PCL-PEG micelles in different cancer therapy has been recorded in countless research for their efficacy as drug cargos. However, systematic studies on the effectiveness of PCL-PEG micelles of specific cancer for pharmaceutical applications are still lacking. As breast cancer is reported as the most prevalent cancer worldwide, we aim to systematically review all available literature that publishes research findings on the PCL-PEG-based micelles as drug cargo for the therapy. We further discussed the preparation method and the anti-tumour efficacy of the micelles. Using prearranged search string, Scopus and Science Direct were selected as the database for the systematic searching strategy. Only eight of the 314 articles met the inclusion requirements and were used for data synthesis. From the review, all studies reported the efficiency of PCL-PEG-based micelles, which act as drug cargo for breast cancer therapy.

A special issue of Essays in Biochemistry on cancer stem cells.

Cancer stem cells (CSCs) are subpopulation of cells within the tumor bulk, which leads to tumor recurrence and therapeutic resistance. Identification of specific CSC targets for detection and efficient cancer therapy are the major hurdles in this research field. In this decade, basic researchers and clinicians made every effort to overcome these challenges to target CSCs using different approaches. This special issue includes a varied collection of review articles with comprehensive discussion on the complexity of CSC heterogeneity, signaling pathways regulating the behaviors of CSCs, the therapeutic resistance mechanism of CSCs, and therapeutic targets against CSCs. These review articles shed light on current advances in understanding of CSC biology.

Engineering cancer cell membrane-camouflaged metal complex for efficient targeting therapy of breast cancer

BackgroundCancer cell membrane-camouflaged nanotechnology for metal complex can enhance its biocompatibility and extend the effective circulation time in body. The ruthenium polypyridyl complex (RuPOP) has extensive antitumor activity, but it still has disadvantages such as poor biocompatibility, lack of targeting, and being easily metabolized by the organism. Cancer cell membranes retain a large number of surface antigens and tumor adhesion molecules CD47, which can be used to camouflage the metal complex and give it tumor homing ability and high biocompatibility.ResultsTherefore, this study provides an electrostatic adsorption method, which uses the electrostatic interaction of positive and negative charges between RuPOP and cell membranes to construct a cancer cell membrane-camouflaged nano-platform (RuPOP@CM). Interestingly, RuPOP@CM maintains the expression of surface antigens and tumor adhesion molecules, which can inhibit the phagocytosis of macrophage, reduce the clearance rate of RuPOP, and increase effective circulation time, thus enhancing the accumulation in tumor sites. Besides, RuPOP@CM can enhance the activity of cellular immune response and promote the production of inflammatory cytokines including TNF-α, IL-12 and IL-6, which is of great significance in treatment of tumor. On the other hand, RuPOP@MCM can produce intracellular ROS overproduction, thereby accelerating the apoptosis and cell cycle arrest of tumor cells to play an excellent antitumor effect in vitro and in vivo.ConclusionIn brief, engineering cancer cell membrane-camouflaged metal complex is a potential strategy to improve its biocompatibility, biological safety and antitumor effects.

Thermal-Responsive MXene-DNA Hydrogel for Near-Infrared Light Triggered Localized Photothermal-Chemo Synergistic Cancer Therapy.

Stimuli-responsive DNA hydrogels are promising candidates for cancer treatment, as they not only possess biocompatible and biodegradable 3D network structures as highly efficient carriers for therapeutic agents but also are capable of undergoing programmable gel-to-solution transition upon external stimuli to achieve controlled delivery. Herein, a promising platform for highly efficient photothermal-chemo synergistic cancer therapy is established by integrating DNA hydrogels with Ti3 C2 TX -based MXene as a photothermal agent and doxorubicin (DOX) as a loaded chemotherapeutic agent. Upon the irradiation of near-infrared light (NIR), temperature rise caused by photothermal MXene nanosheets triggers the reversible gel-to-solution transition of the DOX-loaded MXene-DNA hydrogel, during which the DNA duplex crosslinking structures unwind to release therapeutic agents for efficient localized cancer therapy. Removal of the NIR irradiation results in the re-formation of DNA duplex structures and the hydrogel matrix, and the recombination of free DOX and adaptive hydrogel transformations can also be achieved. As demonstrated by both in vitro and in vivo models, the MXene-DNA hydrogel system, with excellent biocompatibility and injectability, dynamically NIR-triggered drug delivery, and enhanced drug uptake under mild hyperthermia conditions, exhibits efficient localized cancer treatment with fewer side effects to the organisms.

Blend of neem oil based polyesteramide as magnetic nanofiber mat for efficient cancer therapy

Stearic acid-coated magnetic nanoparticles (SMN) and FU (5-Fluorouracil) were immobilized in the blends of neem oil-based polyesteramide and fabricated as nanofiber mat (NM) for controlled release of FU under the influence of an external magnetic field for targeted drug delivery to treat cancer efficiently. Analyzed the surface morphology of the fibers using E-SEM, it was observed that the fibers were smooth with the diameter ranging from 250 to 450 nm. TEM studies showed the uniform distribution of SMN in the nanofibers. The physicochemical properties of NM and raw materials were analyzed using FTIR, TGA, and XRD. The results suggested that the polymers were well blended. In-vitro FU release studies of the NMs recorded a significant difference in the cumulative percentage of FU release from SMN-NMs. The SMN-NMs released 95% of FU in 4 h, whereas, NMs released 83% of FU in 24 h. The cell viability assay for the NM was evaluated in the L929 mouse fibroblast cells, where ˃75% of cells were viable. The hemolysis assay for the developed SMN-NF showed ˂5% of hemolysis, which indicated the NMs were safe for application. The anti-cancer activity of FU loaded SMN-NF was analyzed in the MCF-7 cancer cell line, which recorded more than 50% cell death within 24 h. From SQUID analysis, we found that the 10% SMN were superparamagnetic in nature, the magnetization at 30 kOe was observed to be 4.3 emu/g. Based on the in vitro results, we concluded that the developed SMN-NMs are recommended for in vivo studies to understand their efficacy for the targeted drug delivery to treat cancer.

Versatile Nano-PROTAC-Induced Epigenetic Reader Degradation for Efficient Lung Cancer Therapy.

Recent evidence has indicated that overexpression of the epigenetic reader bromodomain‐containing protein 4 (BRD4) contributes to a poor prognosis of lung cancers, and the suppression of its expression promotes cell apoptosis and leads to tumor shrinkage. Proteolysis targeting chimera (PROTAC) has recently emerged as a promising therapeutic strategy with the capability to precisely degrade targeted proteins. Herein, a novel style of versatile nano‐PROTAC (CREATE ( CR V‐LLC m e mbrane/DS‐PLG A /dB ET 6)) is developed, which is constructed by using a pH/GSH (glutathione)‐responsive polymer (disulfide bond‐linked poly(lactic‐co‐glycolic acid), DS‐PLGA) to load BRD4‐targeted PROTAC (dBET6), followed by the camouflage with engineered lung cancer cell membranes with dual targeting capability. Notably, CREATE remarkably confers simultaneous targeting ability to lung cancer cells and tumor‐associated macrophages (TAMs). The pH/GSH‐responsive design improves the release of dBET6 payload from nanoparticles to induce pronounced apoptosis of both cells, which synergistically inhibits tumor growth in both subcutaneous and orthotopic tumor‐bearing mouse model. Furthermore, the efficient tumor inhibition is due to the direct elimination of lung cancer cells and TAMs, which remodels the tumor microenvironment. Taken together, the results elucidate the construction of a versatile nano‐PROTAC enables to eliminate both lung cancer cells and TAMs, which opens a new avenue for efficient lung cancer therapy via PROTAC.

Folate-modified erythrocyte membrane nanoparticles loaded with Fe3O4 and artemisinin enhance ferroptosis of tumors by low-intensity focused ultrasound.

To overcome the challenges of the low efficiency of artemisinin (ART) in anticancer therapy due to its poor water solubility and poor bioavailability, we constructed folate (FA)-modified erythrocyte membrane (EM)-camouflaged poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) (PFH/ART@PLGA/Fe3O4-eFA). Specifically, the inner core of these NPs is mainly composed of phase-changeable perfluorohexane (PFH), magnetic Fe3O4 and ART. In vitro experiments showed that the prepared PFH/ART@PLGA/Fe3O4-eFA was readily taken up by 4T1 cancer cells. PFH/ART@PLGA/Fe3O4-eFA was exposed to low-intensity focused ultrasound (LIFU) irradiation to induce PFH phase transition and NPs collapse, which promoted the release of ART and Fe3O4. After LIFU irradiation, the proportion of dead 4T1 cells, the level of reactive oxygen species (ROS) and the concentration of intracellular Fe2+ ions in the PFH/ART@PLGA/Fe3O4-eFA group were much higher than those in the other group, indicating that the synergistic effect between the intracellular Fe2+ ions and the released ART played a critical role in tumor cell ferroptosis by enhancing ROS generation in vitro. We demonstrated that FA-modified EM NPs could enhance the targeting and accumulation of the NPs at the tumor site in vivo. After LIFU irradiation at 3 W/m2 for 7 min, tumor growth was completely suppressed through FA-modified EM NPs collapse and the release of ART and Fe3O4, which exerted synergistic effects in inducing tumor ferroptosis. Because of these characteristics, these NPs are considered as a promising approach for the delivery of drugs with poor water solubility for efficient cancer therapy.

A novel gold-polymer-antibody conjugate for targeted (radio-photothermal) treatment of HepG2 cells

Localization of the near-infrared (NIR) plasmonic nanoparticles at the tumor sites is essential for safe and efficient photothermal therapy of cancer. In this work, two biocompatible polymers: modified poly(ethylene glycol) (PEG) and branched polyethyleneimine (bPEI) were used to bind plasmonic hollow gold nanospheres (HAuNS) to the tumor-specific antibody, atezolizumab (ATZ). The photo-immunoconjugate (HAuNS-PEI-PEG-ATZ) was prepared via a simple and cost-effective procedure. The conjugate was also prepared with the radioiodinated antibody (ATZ-131I) to combine the targeted radio- and photothermal cytotoxic actions against human hepatoma (HepG2) cells. In vitro study revealed that attachment to the antibody and the use of cellular internalizing polymers enhanced the cellular localization of both gold and the radiotherapeutic Iodine-131. Compared to bare gold nanoparticles, (HAuNS-PEI-PEG-ATZ) conjugate exhibited a significantly enhanced photothermal ablation of HepG2 cells after laser irradiation (0.4 W cm−2, 5 min). Laser irradiation of the cells treated with the radiolabeled conjugate (HAuNS-PEI-PEG-ATZ-131I) exhibited the highest cytotoxicity against HepG2 cells due to the combinatorial cytotoxic effects.

Multi-Biofunctional Silver-Containing Metallosupramolecular Nanogels for Efficient Antibacterial Treatment and Selective Anticancer Therapy

We develop a simple and efficient route for the fabrication of water-soluble metallosupramolecular polymers. We demonstrate that the introduction of environment-responsive metal-organic complexes within supramolecular polymers endows the resulting self-assembled nano-objects with outstanding antibacterial activity and may significantly improve the efficacy and safety of selective cancer therapy. Herein, we successfully developed a silver-containing supramolecular polymer (Ag-Cy-J) possessing a hydrophilic Jeffamine backbone and highly sensitive pH-responsive cytosine-silver-cytosine (Cy-Ag-Cy) linkages, which spontaneously self-assemble to produce sterically stabilized spherical nanogels in water. The resulting nanogels exhibit several attractive features such as unique fluorescence behavior in water, highly stable self-assembled structures in biological media, significant antihemolytic capability, highly sensitive pH-responsiveness and broad-spectrum antibacterial activity against various bacteria strains. Importantly, in vitro cellular assays clearly demonstrated Ag-Cy-J nanogels highly selectively target and induce cytotoxicity in cancer cells, without affecting normal cells. The selective cytotoxic activity in cancer cells is attributed to rapid dissociation of the Cy-Ag-Cy complexes within the nanogels in the cancer cell microenvironment, followed by the intracellular release of silver ions and induction of rapid, massive apoptosis. Overall, the pH-sensitive Cy-Ag-Cy complexes within this supramolecular nanogel system may provide a route to remarkably improve the efficacy of both antibacterial and cancer drug therapies. Statement of significanceWe present a significant breakthrough in the development of a water-soluble silver-containing metallosupramolecular polymer (Ag-Cy-J) that spontaneously self-assembles in water into a spherical nanogel with unique physical characteristics due to the existence of highly sensitive pH-responsive cytosine-silver-cytosine (Cy-Ag-Cy) linkages within the nanogels. Importantly, a series of in vitro antibacterial and anticancer assays demonstrated the Ag-Cy-J nanogels not only exert strong antibacterial activity against various bacterial strains, but also exhibit a high degree of selective uptake and rapidly induce massive apoptosis in cancer cells without harming normal cells. Thus, this newly discovered supramolecular system may potentially provide a multi-biofunctional soft nanomaterial for efficient and safe antibacterial and cancer therapies.

A reactive oxygen species-replenishing coordination polymer nanomedicine disrupts redox homeostasis and induces concurrent apoptosis-ferroptosis for combinational cancer therapy

Reactive oxygen species (ROS) are important signal molecules and imbalanced ROS level could lead to cell death. Elevated ROS levels in tumor tissues offer an opportunity to design ROS-responsive drug delivery systems (DDSs) or ROS-based cancer therapies such as chemodynamic therapy. However, their anticancer efficacies are hampered by the ROS-consuming nature of these DDSs as well as the high concentration of reductive agents like glutathione (GSH). Here we developed a doxorubicin (DOX)-incorporated iron coordination polymer nanoparticle (PCFD) for efficient chemo-chemodynamic cancer therapy by using a cinnamaldehyde (CA)-based ROS-replenishing organic ligand (TCA). TCA can ROS-responsively release CA to supplement intracellular ROS and deplete GSH by a thiol-Michael addition reaction, which together with DOX-triggered ROS upregulation and Fe3+-enabled GSH depletion facilitated efficient DOX release and enhanced Fenton reaction, thereby inducing redox dyshomeostasis and cancer cell death in a concurrent apoptosis-ferroptosis way. Both in vitro and in vivo studies revealed that ROS-replenishing PCFD exhibited much better anticancer effect than ROS-consuming control nanoparticle PAFD. The ingenious ROS-replenishing strategy could be expanded to construct versatile ROS-responsive DDSs and ROS-based nanomedicines with potentiated anticancer activity. Statement of significanceWe develop a doxorubicin (DOX)-incorporated iron coordination polymer nanoparticle (PCFD) for efficient chemo-chemodynamic cancer therapy by using a cinnamaldehyde-based reactive oxygen species (ROS)-replenishing organic ligand. This functional ligand can ROS-responsively release cinnamaldehyde to supplement intracellular H2O2 and deplete glutathione (GSH) by a thiol-Michael addition reaction, which together with DOX-triggered ROS upregulation and Fe3+-enabled GSH depletion facilitates efficient DOX release and enhanced Fenton reaction, thereby inducing redox dyshomeostasis and cancer cell death in a concurrent apoptosis-ferroptosis way. Both in vitro and in vivo studies reveal that ROS-replenishing PCFD exhibit much better anticancer effect than ROS consuming counterpart. This study provides a facile and straightforward strategy to design ROS amplifying nanoplatforms for cancer treatment.

Radiofrequency-thermal effect of cisplatin-crosslinked nanogels for triple therapies of ablation-chemo-embolization

Improving the synergistic effect of radiofrequency ablation (RFA) and trans-artery chemo-embolization (TACE) remains the main challenge in interventional cancer therapy. The present study reports cisplatin-crosslinking poly(N-isoprylacrylamide-b-methyl acrylic acid) nanogels (Pt-PNA) based on the RF-thermal effect of cisplatin as the RF-responsive embolic nano-platform that acts via coordination bonding between Pt(II) ions and carboxyl, thereby triggering cell apoptosis, necrosis, and metastasis inhibition. Moreover, Pt-PNA might diffuse rapidly into tumor peripheral arteries and block the tumor blood supply facilitated by temperature-sensitive sol–gel transition, thereby achieving efficient TACE cancer therapy. The antitumor efficacy exhibited in vivo by Pt-PNA indicated that the radiofrequency-responsive Pt-PNA greatly improved the hypoxic tumor microenvironment after the TAE procedure, thereby inducing a favorable immune response and enhancing the synergistic antitumor effect of RFA and TACE.

Modulation of the Tumor Immune Microenvironment by Bi2 Te3 -Au/Pd-Based Theranostic Nanocatalysts Enables Efficient Cancer Therapy.

Nanozymes with multienzyme-mimicking activities have shown great potential in cancer therapy due to their ability to modulate the complex tumor microenvironment (TME). Herein, a second near-infrared (NIR-II) photothermal-nanocatalyst by decorating Bi2 Te3 nanosheets with ultrasmall Au/Pd bimetallic nanoparticles (Bi2 Te3 -Au/Pd) to reverse the immunosuppressive TME is developed. The peroxidase (POD)-like and catalase (CAT)-like activities, and glutathione (GSH) consumption capacity of Au/Pd modulates the TME by disrupting the intracellular redox homeostasis and relieving hypoxia in the TME. Notably, the amplified oxidative stress induces the accumulation of lipid hydroperoxides (LPO) for enhanced ferroptosis. Moreover, upon NIR-II photoirradiation at 1064nm, the localized heat generated by Bi2 Te3 not only directly ablates the cancer cells but also enhances the Au/Pd-mediated catalysis-mediated cancer therapy. Furthermore, both in vitro and in vivo studies confirm that the Bi2 Te3 -Au/Pd nanocatalysts (BAP NCs) can effectively suppress tumor growth by inducing immunogenic cell death (ICD), and suppressing metastasis and recurrence by the synergistic treatment. Overall, this study provides a promising theranostic strategy for effective tumor inhibition.

PD-L1-Targeted Co-Delivery of Two Chemotherapeutics for Efficient Suppression of Skin Cancer Growth.

To overcome the severe side effects of cancer chemotherapy, it is vital to develop targeting chemotherapeutic delivery systems with the potent inhibition of tumour growth, angiogenesis, invasion and migration at low drug dosages. For this purpose, we co-loaded a conventional antiworm drug, albendazole (ABZ), and a TOPK inhibitor, OTS964, into lipid-coated calcium phosphate (LCP) nanoparticles for skin cancer treatment. OTS- and ABZ-loaded LCP (OTS-ABZ-LCP) showed a synergistic cytotoxicity against skin cancer cells through their specific cancerous pathways, without obvious toxicity to healthy cell lines. Moreover, dual-targeting the programmed death ligand-1 (PD-L1) and folate receptor overexpressed on the surface of skin cancer cells completely suppressed the skin tumour growth at low doses of ABZ and OTS. In summary, ABZ and OTS co-loaded dual-targeting LCP NPs represent a promising platform with high potentials against complicated cancers where PD-L1/FA dual targeting appears as an effective approach for efficient and selective cancer therapy.

A novel cascaded energy conversion system inducing efficient and precise cancer therapy.

Cancer therapies based on energy conversion, such as photothermal therapy (PTT, light-to-thermal energy conversion) and photodynamic therapy (PDT, light-to-chemical energy conversion) have attracted extensive attention in preclinical research. However, the PTT-related hyperthermia damage to surrounding tissues and shallow penetration of PDT-applied light prevent further advanced clinical practices. Here, we developed a thermoelectric therapy (TET) based on thermoelectric materials constructed p-n heterojunction (SrTiO3/Cu2Se nanoplates) on the principle of light-thermal-electricity-chemical energy conversion. Upon irradiation and natural cooling-induced the temperature gradient (35–45 oC), a self-build-in electric field was constructed and thereby facilitated charges separation in bulk SrTiO3 and Cu2Se. Importantly, the contact between SrTiO3 (n type) and Cu2Se (p type) constructed another interfacial electric field, further guiding the separated charges to re-locate onto the surfaces of SrTiO3 and Cu2Se. The formation of two electric fields minimized probability of charges recombination. Of note, high-performance superoxide radicals and hydroxyl radicals’ generation from O2 and H2O under catalyzation by separated electrons and holes, led to intracellular ROS burst and cancer cells apoptosis without apparent damage to surrounding tissues. Construction of bulk and interfacial electric fields in heterojunction for improving charges separation and transfer is also expected to provide a robust strategy for diverse applications.

Glutathione-depleted and cancer-targeted nanocapsules encapsulating bimetallic oxide nanoparticles for enhanced chemo-sonodynamic therapy

Sonodynamic therapy (SDT) has emerged as a promising noninvasive therapeutic modality due to its deep tissue penetration depth. Herein, biodegradable poly(lactic-co-glycolic acid) (PLGA) nanocapsules encapsulating oxygen-deficient MnWOx nanoparticles (NPs) and doxorubicin (DOX) were fabricated for chemo-sonodynamic combination therapy against cancer. To achieve cancer-targeted chemo-SDT, PLGA was conjugated to a cancer-targeting biotin through poly(ethylene glycol) (PEG). Biotin-PEG-PLGA (BP-PLGA) nanocapsules encapsulating DOX and hydrophobic MnWOx NPs (BP-PLGA-DOX@MnWOx) exhibited high physiological stability and pH-responsive drug release. The oxygen-deficient MnWOx NPs enabled US-triggered generation of singlet oxygen and hydroxyl radicals owing to their oxygen-deficient structures that prevent electron–hole recombination. Glutathione (GSH) depletion by MnWOx-loaded PLGA nanocapsules was observed in MCF-7 human breast cancer cells, which leads to augmented intracellular ROS levels and sonodynamic effects. Notably, BP-PLGA-DOX@MnWOx greatly improved cellular uptake by breast cancer cells, resulting in efficient intracellular delivery of DOX and MnWOx NPs. As a result, BP-PLGA-DOX@MnWOx exhibited efficient and cancer-targeted cytotoxicity in MCF-7 cells upon US irradiation. This study demonstrates that BP-PLGA-DOX@MnWOx nanocapsules are promising cancer-targeting nanosonosensitizers for efficient chemo-sonodynamic cancer therapy.

A NTR and O2 programmed responsive photogenic radicals for efficient hypoxia cancer therapy

Stimulus responsive photodynamic therapy has attracted much attention. Although many methods have been proposed to alleviate the impact of hypoxia on photodynamic therapy (PDT), hypoxia is still one of the biggest obstacles to the efficient photodynamic treatment of tumors. Herein, a novel kind of nitroreductase (NTR) and O2 programmed responsive photosensitizer Eos-NO2 was developed to achieve precise and efficient PDT of hypoxia tumor. Specifically, the PDT “off” state Eos-NO2 was activated by the overexpressed NTR in tumor region to form PDT “on” state Eos. Then, the produced Eos in hypoxia could further generate the active free radicals and singlet oxygen for the efficient treatment of hypoxic tumors owing to photo-induced free radical process. Both in vitro and in vivo results confirm that such a NTR and O2 programmed responsive photosensitizer Eos-NO2 shows high specificity and selectivity for hypoxic solid tumor, presenting good prospects in the clinical cancer phototherapy.

Biodegradable Amorphous Copper Iron Tellurite Promoting the Utilization of Fenton-Like Ions for Efficient Synergistic Cancer Theranostics.

The major hurdles of chemodynamic therapy (CDT) are nondegradability and low-efficiency utilization of chemodynamic agents, and intracellular glutathione (GSH)-induced rapid scavenging of hydroxyl radicals (•OH). Here, a biodegradable a-CFT@IP6@BSA agent is reported for efficient cancer therapy by encapsulating amorphous copper iron tellurite nanoparticles (a-CFT NPs) into inositol hexaphosphate (IP6) and bovine serum albumin (BSA). The biggest merits of this agent are the GSH responsive degradation and amorphous structure, allowing the tumor-specific release of plenty of Cu+ ions and their high-efficiency utilization for •OH production via the Fenton-like reaction. Besides, the released Cu+ ions can deplete the intracellular GSH and thereby protect •OH from scavenging, greatly improving the CDT efficiency. Further, it is found that the a-CFT@IP6@BSA NP treatment down-regulates the levels of glutathione peroxidase 4 and BCL-2, indicating GSH depletion-associated ferroptosis and IP6-induced apoptotic death of cancer cells. Utilizing the T1/T2 dual-modal magnetic resonance imaging capability, the a-CFT@IP6@BSA NPs are demonstrated with excellent in vivo anticancer efficiency and have great potential for imaging-guided cancer treatment.

Codelivery of π-π Stacked Dual Anticancer Drugs Based on Aloe-Derived Nanovesicles for Breast Cancer Therapy.

To overcome the low efficacy of conventional monotherapeutic approaches that use a single drug, functional nanocarriers loaded with an amalgamation of anticancer drugs have been promising in cancer therapy. Herein, aloe-derived nanovesicles (gADNVs) are modified with an active integrin-targeted peptide (Arg-Gly-Asp, RGD) by the postinsertion technique to deliver indocyanine green (ICG) and doxorubicin (DOX) for efficient breast cancer therapy. We presented for the first time that the π-π stacking interaction can turn the "competitive" relationship of ICG and DOX inside gADNVs into a "cooperative" relationship and enhance their loading efficiency. The dual-drug codelivery nanosystem, denoted as DIARs, was well stable and leakproof, exhibiting high tumor-targeting capability both in vitro and in vivo. Meanwhile, this nanosystem showed significant inhibition of cell growth and migration and induced cell apoptosis with the combination of phototherapy and chemotherapy. Intravenous administration of DIARs exhibited high therapeutic efficacy in a 4T1 tumor-bearing mouse model and exhibited no obvious damage to other organs. Overall, our DIAR nanosystem constitutively integrated the natural and economical gADNVs, π-π stacking interaction based on efficient drug loading, and tumor-targeted RGD modification to achieve an effective combination therapy for breast cancer.

Biomimetic metal–organic frameworks navigated biological bombs for efficient lung cancer therapy

The rising risk of lung cancer has become a primary global concern with high mortality and mobility. Presently, clinically used anticancer drugs show limited efficacy and significant side effects. A new generation of anticancer weapons is in great demand for lung cancer therapy. Herein, we have developed a novel style of biomimetic zeolitic imidazolate framework-8 (ZIF-8) based on the merits of cell membranes derived from human bone marrow mesenchymal stem cells (hBMSCs), which can navigate biological bombs herpes simplex virus type I thymidine kinase-encoded plasmids (pHSVtk) and ganciclovir (GCV) to treat lung cancer. The biological bomb-loaded structure can kill transfected lung cancer cells and neighboring lung cancer cells through the “bystander effect,” which induces efficient suppression of lung cancer both in vitro and in vivo. The biomimetic nanoparticles show an enhanced circulation lifetime and drug accumulation in the tumor tissues and significantly inhibit the tumors. We have developed a straightforward approach to deliver biological bombs with biomimetic metal–organic frameworks for efficient lung cancer therapy. To the best of our knowledge, this is the first report of such a strategy for lung cancer therapy.