Synergistic Cancer Treatment Research Articles

Living Therapeutics for Synergistic Hydrogen-Photothermal Cancer Treatment by Photosynthetic Bacteria.

Hydrogen gas (H2) therapy, recognized for its inherent biosafety, holds significant promise as an anti-cancer strategy. However, the efficacy of H2 treatment modalities is compromised by their reliance on systemic gas administration or chemical reactions generation, which suffers from low efficiency, poor targeting, and suboptimal utilization. In this study, living therapeutics are employed using photosynthetic bacteria Rhodobacter sphaeroides for in situ H2 production combined with near-infrared (NIR) mediated photothermal therapy. Living R. sphaeroides exhibits strong absorption in the NIR spectrum, effectively converting light energy into thermal energy while concurrently generating H2. This dual functionality facilitates the targeted induction of tumor cell death and substantially reduces collateral damage to adjacent normal tissues. The findings reveal that integrating hydrogen therapy with photothermal effects, mediated through photosynthetic bacteria, provides a robust, dual-modality approach that enhances the overall efficacy of tumor treatments. This living therapeutic strategy not only leverages the therapeutic potential of both hydrogen and photothermal therapeutic modalities but also protects healthy tissues, marking a significant advancement in cancer therapy techniques.

Multi‐Enzyme Mimetic MoCu Dual‐Atom Nanozyme Triggering Oxidative Stress Cascade Amplification for High‐Efficiency Synergistic Cancer Therapy

AbstractSingle‐atom nanozymes (SAzymes) with ultrahigh atom utilization efficiency have been extensively applied in reactive oxygen species (ROS)‐mediated cancer therapy. However, the high energy barriers of reaction intermediates on single‐atom sites and the overexpressed antioxidants in the tumor microenvironment restrict the amplification of tumor oxidative stress, resulting in unsatisfactory therapeutic efficacy. Herein, we report a multi‐enzyme mimetic MoCu dual‐atom nanozyme (MoCu DAzyme) with various catalytic active sites, which exhibits peroxidase, oxidase, glutathione (GSH) oxidase, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase mimicking activities. Compared with Mo SAzyme, the introduction of Cu atoms, formation of dual‐atom sites, and synergetic catalytic effects among various active sites enhance substrate adsorption and reduce the energy barrier, thereby endowing MoCu DAzyme with stronger catalytic activities. Benefiting from the above enzyme‐like activities, MoCu DAzyme can not only generate multiple ROS, but also deplete GSH and block its regeneration to trigger the cascade amplification of oxidative stress. Additionally, the strong optical absorption in the near‐infrared II bio‐window endows MoCu DAzyme with remarkable photothermal conversion performance. Consequently, MoCu DAzyme achieves high‐efficiency synergistic cancer treatment incorporating collaborative catalytic therapy and photothermal therapy. This work will advance the therapeutic applications of DAzymes and provide valuable insights for nanocatalytic cancer therapy.

H2O2 Self-Supplying CaO2 Nanoplatform Induces Ca2+ Overload Combined with Chemodynamic Therapy to Enhance Cancer Immunotherapy.

Integrating chemodynamic therapy (CDT) with Ca2+ overload offers a potent strategy for enhancing cancer immunotherapy. However, the effectiveness of this approach is significantly constrained by the scarce availability of H2O2 in solid tumors. Here, we engineered a nanoplatform based on CaO2 nanoparticles (NPs) capable of encapsulating curcumin (CUR) and self-supplying H2O2 for synergistic CDT-augmented antitumor immunotherapy (CaO2@CUR@ZIF-Cu, denoted as CCZC). In the acidic tumor microenvironment, CCZC disintegrated to release CUR and copper(II) ions (Cu2+), revealing the core CaO2 NPs. CDT was amplified by escalating hydroxyl radical (•OH) production through a Fenton-like reaction mediated by H2O2 from the hydrolysis of CaO2 NPs. Ca2+ sourced from CaO2 NPs and CUR, an initiator of Ca2+ overload, induced Ca2+ overload in tumor cells, thereby promoting apoptosis. Subsequently, apoptotic tumor cells released tumor-associated antigens and pro-inflammatory cytokines, triggering adaptive immune responses and enhancing antitumor immunotherapy effects. In vivo experiments demonstrated that the intratumoral administration of CCZC displayed significant inhibitory effects, with an inhibition rate of up to 78% on B16-OVA-tumor-bearing mice compared to untreated. Moreover, an elevated proportion of mature dendritic cells were observed in the tumor-draining lymph nodes, along with an increase in cytotoxic T lymphocytes in the spleen. These findings suggest that our engineered nanoplatform effectively curtailed tumor growth via enhanced cancer immunotherapy by synergizing Ca2+ overload and CDT, proposing a novel strategy for synergistic cancer treatment.

Cell membrane camouflaged Cu-doped mesoporous polydopamine for combined CT/PTT/CDT synergistic treatment of breast cancer

Currently, traditional monotherapy for cancer often results in indiscriminate attacks on the body, leading to the emergence of new health problems. To confront these challenges, multimodal combination therapy has become necessary. However, how to develop new smart nanomaterials through green synthesis methods, delivering drugs while simultaneously synergizing multimodal combination therapies for tumor treatment, remains a topic of great significance. In this study, a biomimetic composite nanomaterial (RM-Cu/P) composed of mesoporous polydopamine (MPDA) as the core and red blood cell membranes (RBCMs) as the shell was synthesized as a drug carrier to deliver doxorubicin (DOX) while achieving synergistic chemotherapy, photothermal and chemodynamic therapy (CT/PTT/CDT). Herein, the nanoparticles were extensively characterized to examine their morphological characteristics, elemental composition, and drug-carrying capacity. Notably, the coating of RBCM reduced the toxicity of the RM-Cu/P@DOX nanoparticles, improved their targeting ability and prolonged their circulation time in vivo. The Cu-doped nanoparticles were capable of initiating a Fenton-like reaction to generate reactive oxygen species (ROS) for CDT, while the photothermal conversion efficiency (η) reached 45.20 % under NIR laser irradiation. Subsequently, the particles were examined by in vivo and in vitro experimental studies in cytotoxicity, cellular uptake, ROS levels, lysosomal escape, and mouse tumor model to evaluate their potential application in antitumor. Compared with monotherapy, the RM-Cu/P@DOX nanoparticles had multiple-stimulation response properties under redox, pH, and NIR, which exhibited the advantage of combined trimodal therapy, resulting in remarkable synergistic antitumor efficacy. In conclusion, this innovative platform exhibited promising applications in smart drug delivery and synergistic treatment of cancer.

Photothermal amplified multizyme activity for synergistic photothermal-catalytic tumor therapy

Nano-enzymatic catalytic therapy has been widely explored as a promising tumor therapeutic method with specific responsiveness to the tumor microenvironment (TME). However, the inherent lower and simplex catalytic efficiency impairs their anti-tumor efficacy. Therefore, developing novel nanozymes with relatively high and multiple catalytic characteristics, simultaneously enhancing the enzyme-like activity of nanozymes using the proper method, photothermal promoted catalytic property, is a reliable way. In this paper, we report a manganese oxide/nitrogen-doped carbon composite nanoparticles (MnO-N/C NPs) with multi-enzyme mimetic activity and photothermal conversional effect. The peroxidase (POD)-like/oxidase (OXD)-like/catalase (CAT)-like activity of MnO-N/C nanozymes was accelerated upon exposure to an 808 nm NIR laser. In vitro and in vivo results proved that the MnO-N/C NPs shown excellent magnetic resonance imaging (MRI) guided synergistic photothermal-enhanced catalytic treatment and photothermal therapy of liver cancer. The photothermal enhanced multi-enzyme activity maximizes the efficacy of catalytic and photothermal therapy while reducing harm to healthy cells, thereby offering valuable insights for the development of next-generation photothermal nanozymes to enhance tumor therapy.

NIR‐Triggered Cu2O/Cu2‐xS Heterostructure as an “All‐In‐One” Functional Nanoplatform for Efficient Synergistic Tumor Therapy

AbstractThe fabrication of synergistic multifunctional anti‐tumor nanoplatforms is challenging due to the urgent requirement to activate different therapeutic modalities. Although the multi‐modal treatments can be achieved by carrying out the activation with different exogenous and endogenous stimulations in sequence, this tedious manner is not applicable to the ideal synergistic cancer treatment. Herein, a simple heterojunction of Cu2O/Cu2‐xS modified with gambogic acid and hyaluronic acid (CCS@GA@HA) is ingeniously fabricated for the synergistic cancer treatment combining photothermal therapy (PTT), photocatalytic therapy (PCT), chemodynamic therapy (CDT) and potential ferroptosis just activated by the single near infrared (NIR) light irradiation. Cu2O/Cu2‐xS heterostructure (CCS) with promoted separation and transfer efficiency of photogenerated charge carriers exhibits excellent photocatalytic performance. The intervention of gambogic acid (GA) downregulates the overexpression of heat shock protein 90 (HSP90), which make it possible to execute the mild PTT. And the CDT performance is efficiently improved by the heat generated from PTT. Specifically, CCS appears to accelerate the accumulation of lipid peroxides (LPO) and inactivate glutathione peroxidase 4 (GPX4) that directly induce ferroptosis. In brief, CCS@GA@HA exhibits prominent NIR‐triggered synergistic effect involving PCT, mild PTT, enhanced CDT and ferroptosis for an effective multi‐modal tumor treatment.

Cu0-based nanoparticles boost anti-tumor efficacy via synergy of cuproptosis and ferroptosis enhanced by cuproptosis-induced glutathione synthesis disorder

Apoptotic resistance of tumor often leads to poor efficacy from mono-therapy based on apoptosis. Cuproptosis, a new type of non-apoptotic cell death related to mitochondrial dysfunction, can alter metabolism and enhance ferroptosis, providing a promising strategy for effective synergistic cancer treatment. In this work, Cu0-based nanoparticles (denoted as HA-ZCu) were successfully developed to improve anti-tumor efficacy by combining cuproptosis with enhanced ferroptosis, which was achieved by cuproptosis-induced glutathione synthesis disorder. In vitro studies revealed that HA-ZCu effectively induced cuproptosis and ferroptosis in HepG2 cells. Moreover, HA-ZCu induced mitochondrial dysfunction and decreased intracellular adenosine triphosphate (ATP), glutamate, and glutathione, demonstrating the effective synergy. In vivo studies further approved the synergistic therapeutic efficacy of HA-ZCu, where the inhibition rate of tumor growth reached 83.2 %. This work represents the first example of enhanced anti-tumor efficacy via cuproptosis and ferroptosis synergy through cuproptosis-induced glutathione synthesis disorder.

Harnessing transcription factor-driven ROS for synergistic multimodal lung cancer treatment

Multimodal treatment of cancer is an unstoppable revolution in clinical application. However, designing a platform that integrates therapeutic modalities with different pharmacokinetic characteristics remains a great challenge. Herein, we designed a universal lipid nanoplatform equipping a ROS-cleavable docetaxel prodrug (DTX-L-DTX) and an NF-E2-related factor 2 (NRF2) inhibitor (clobetasol propionate, CP). This simply fabricated nanomedicine enables superior synergistic molecularly targeted/chemo/radio therapy for lung cancer cascade by a transcription factor-driven ROS self-sustainable motion. Chemotherapy is launched via ROS-triggered DTX release. Subsequently, CP inhibits the expression of NRF2 target genes, resulting in efficient targeted therapy, meanwhile inducing sustained ROS generation which in turn facilitates chemotherapy by overcoming ROS consumption during the DTX release process. Finally, the introduction of radiotherapy further amplifies ROS, offering continuous mutual feedback to amplify the ultimate treatment performance. This strategy is conceptually and operationally simple, providing solutions to challenges in clinical cancer treatment and beyond.

Dual-Targeting Nanoplatform Based on Rolling Circle Amplification for Enhanced Multimodal Synergistic Treatment of Breast Cancer

Dual-Targeting Nanoplatform Based on Rolling Circle Amplification for Enhanced Multimodal Synergistic Treatment of Breast Cancer

Near infrared light and tumor microenvironment multi-sensitive “Yolk-Shell MOF Nanoreactor” for synergistic treatment of cervical cancer

Developing novel and efficient multimodal nanomaterial-based anticancer agents to meet complex clinical demands is an urgent challenge. Herein, novel graphene quantum dots (GQDs) doped Cu2S@ZIF-8 yolk-shell Metal-Organic Frameworks (MOFs) was firstly constructed by a simple and mild wet-chemical method at room temperature. The MOFs possessed exiting photothermal performance and catalytic activities, which were further enhanced greatly upon near infrared light irradiation or in tumor microenvironment (TME) due to their unique composition and structure. The possible mechanism was discussed. The introduction of GQDs played a key role because it could effectively absorb NIR light and convert partial Cu2S nanodots to CuS nanodots, thus further increase NIR light absorption and generate cascaded electron transport effects, which will enhanced the photothermal performance and catalytic activities of yolk-shell MOFs. After small molecules drugs doxorubicin (DOX) and folic acid (FA) were loaded and conjugated, the as-prepared MOFs could be expected as efficient nanoplatform for cervical cancer synergistic therapy. These prominent intelligent laser and tumor microenvironment (TME)-responsive features of yolk-shell nanocomposite provide an innovative paradigm to explore nanoplatform for tumor therapy.

Engineering PD-L1 targeted liposomal canagliflozin achieves multimodal synergistic cancer therapy

Immunotherapy-involved combination cancer therapy heralds an unstoppable revolution in clinical practice. However, designing a streamlined approach to integrate immunotherapy with other therapies remains a formidable challenge. Canagliflozin, a clinical drug for type II diabetes, has gained growing interest in cancer therapy, albeit its precise mechanism remains largely elusive. Here, we delve into the multifaceted antitumor mechanisms of canagliflozin, including co-suppression of MAPK/ERK and PI3K/AKT signaling pathways, induction of PD-L1 degradation via ubiquitination and sensitization to X-ray irradiation via downregulation of DNA damage repair-related molecules, thereby offering opportunities for synergistic cancer treatment. For this purpose, we designed a universal nanoliposome coated with a PD-L1-targeting peptide to efficiently deliver canagliflozin in vivo. This simple fabricated nanodrug exhibited specific tumor-targeting ability and excellent biosafety. In vivo anti-cancer efficacy evaluation revealed synergistic pathway-targeted therapy from canagliflozin and immunotherapy facilitated by both canagliflozin and peptide. Furthermore, the introduction of radiotherapy further augmented the overall treatment performance. This study will revisit the diverse anti-tumor mechanisms of canagliflozin and its potential in cancer therapy, greatly expanding its clinical indication. In addition, the targeted delivery system of canagliflozin developed in this study will achieve multimodal synergistic cancer therapy, providing solutions to challenges in clinical cancer treatment and beyond.

Hyaluronic acid-coated porphyrin nanoplatform with oxygen sustained supplying and glutathione depletion for enhancing photodynamic/ion/chemo synergistic cancer treatment

Hypoxia and high concentration of glutathione (GSH) in tumor seriously hinder the role of reactive oxygen species (ROS) and oxygen-dependence strategy in tumor treatment. In this work, a self-generating oxygen and self-consuming GSH hyaluronic acid (HA)-coated porphyrin nanoplatform (TAPPP@CaO2/Pt(IV)/HA) is established for enhancing photodynamic/ion/chemo targeting synergistic therapy of tumor. During the efforts of ROS production by nanosystems, a GSH consuming strategy is implemented for augmenting ROS-induced oxidative damage for synergetic cancer therapy. CaO2 in the nanosystems is decomposed into O2 and H2O2 in an acidic environment, which alleviates hypoxia and enhances the photodynamic therapy (PDT) effect. Calcium overload causes mitochondria dysfunction and induces apoptosis. Pt (IV) reacts with GSH to produce Pt (II) for chemotherapy and reduce the concentration of GSH, protecting ROS from scavenging for augmenting ROS-induced oxidative damage. In vitro and in vivo results demonstrated the self-generating oxygen and self-consuming GSH strategy can enhance ROS-dependent PDT coupled with ion/chemo synergistic therapy. The proposed strategy not only solves the long-term problem that hypoxia limits therapeutic effect of PDT, but also ameliorates the highly reducing environment of tumors. Thus the preparation of TAPPP@CaO2/Pt(IV)/HA provided a novel strategy for the effective combined therapy of cancers.

Iron Oxide Nanoparticles: Parameters for Optimized Photoconversion Efficiency in Synergistic Cancer Treatment.

Photothermal therapy (PTT) can overcome cancer treatment resistance by enhancing the cell membrane permeability, facilitating drug accumulation, and promoting drug release within the tumor tissue. Iron oxide nanoparticles (IONPs) have emerged as effective agents for PTT due to their unique properties and biocompatibility. Approved for the treatment of anemia, as MRI contrast agents, and as magnetic hyperthermia mediators, IONPs also offer excellent light-to-heat conversion and can be manipulated using external magnetic fields for targeted accumulation in specific tissue. Optimizing parameters such as the laser wavelength, power density, shape, size, iron oxidation state, functionalization, and concentration is crucial for IONPs' effectiveness. In addition to PTT, IONPs enhance other cancer treatment modalities. They improve tumor oxygenation, enhancing the efficacy of radiotherapy and photodynamic therapy. IONPs can also trigger ferroptosis, a programmed cell death pathway mediated by iron-dependent lipid peroxidation. Their magneto-mechanical effect allows them to exert a mechanical force on cancer cells to destroy tumors, minimizing the damage to healthy tissue. This review outlines strategies for the management of the photothermal performance and PTT efficiency with iron oxide nanoparticles, as well as synergies with other cancer therapies.

Synergistic Treatment of Breast Cancer by Combining the Antimicrobial Peptide Piscidin with a Modified Glycolipid.

Piscidin 3 (P3), a peptide produced by fish, and a hexyl ester-modified sophorolipid (SL-HE), have individually shown promise as antimicrobial and anticancer drugs. A recent report by our team revealed that combining P3 with SL-HE in a 1:8 molar ratio resulted in an 8-fold enhancement in peptide activity, while SL-HE improved by 25-fold its antimicrobial activity against the Gram-positive microorganism Bacillus cereus. Extending these findings, the same P3/SL-HE combination was assessed on two breast cancer cell lines: BT-474, a hormonally positive cell line, and MDA-MB-231, an aggressive triple-negative cell line. The results demonstrated that the 1:8 molar ratio of P3/SL-HE synergistically enhances the anticancer effects against both tumorigenic breast cell lines. Mechanistic studies indicate the activation of an intrinsic apoptotic cell death mechanism through an increase in reactive oxygen species and mitochondrial dysfunction and a secondary programmed necrotic pathway that involves pore formation in the plasma membrane. When a fibroblast cell line, CCD1065SK HDF, was utilized to determine selectivity, the synergistic SL-HE/P3 combination exhibited a protective property compared to the use of SL-HE alone and therefore afforded vastly improved selectivity indices. Given the promising results reported herein, the synergistic combination of P3/SL-HE constitutes a novel strategy that merits further study for the treatment of breast cancer.

Curcumin and Baicalin Co-Loaded Nanoliposomes for Synergistic Treatment of Non-Small Cell Lung Cancer.

Currently, the treatment of patients with advanced non-small cell lung cancer (NSCLC) mainly relies on traditional chemotherapeutic drugs; however, most of them have limited therapeutic effects and high toxicity. Some natural products with good therapeutic efficacy and low toxicity and side effects are limited in clinical application due to their low solubility and bioavailability. In this study, a nanoliposome drug-carrying system (Lip-Cur/Ba) was developed for the co-delivery of curcumin (Cur) and baicalin (Ba) using the thin-film hydration method. In vitro experiments demonstrated that Lip-Cur/Ba had a strong killing effect on A549 cells, and the inhibitory effect of Lip-Cur/Ba on A549 cells was enhanced by 67.8% and 51.9% relative to that of the single-carrier system, which could reduce the use of a single-drug dose (Lip-Cur and Lip-Ba), delay the release rate of the drug and improve the bioavailability. In vivo experiments demonstrated the antitumor activity of Lip-Cur/Ba by intravitreal injection in BALB/c mice, and there were no obvious toxic side effects. This study provides a new idea for curcumin and baicalin to be used in the co-treatment of NSCLC by constructing a new vector.

Biodegradable Ruthenium-Rhenium Complexes Containing Nanoamplifiers: Triggering ROS-Induced CO Release for Synergistic Cancer Treatment.

The constrained effectiveness of photodynamic therapy (PDT) has impeded its widespread use in clinical practice. Urgent efforts are needed to address the shortcomings faced in photodynamic therapy, such as photosensitizer toxicity, short half-life, and limited action range of reactive oxygen species (ROS). In this study, a biodegradable copolymer nanoamplifier is reported that contains ruthenium complex (Ru-complex) as photosensitizer (PS) and rhenium complex (Re-complex) as carbon monoxide (CO)-release molecule (CORM). The well-designed nanoamplifier brings PS and CORM into close spatial proximity, significantly promotes the utilization of light-stimulated reactive oxygen species (ROS), and cascaded amplifying CO release, thus enabling an enhanced synergistic effect of PDT and gas therapy for cancer treatment. Moreover, owing to its intrinsic photodegradable nature, the nanoamplifier exhibits good tumor accumulation and penetration ability, and excellent biocompatibility in vivo. These findings suggest that the biodegradable cascaded nanoamplifiers pave the way for a synergistic and clinically viable integration of photodynamic and gas therapy.

Bottle Nanomotors Amplify Tumor Oxidative Stress for Enhanced Calcium Overload/Chemodynamic Therapy.

Developingmultifunctional, stimuli-responsive nanomedicine isintriguing because ithasthepotential toeffectively treat cancer. Yet, poor tumor penetration of nanodrugs results in limited antitumor efficacy. Herein, an oxygen-driven silicon-based nanomotor (Si-motor) loaded with MnO and CaO2 nanoparticles is developed, which can move in tumor microenvironment (TME) by the cascade reaction of CaO2 and MnO. Under acidic TME, CaO2 reacts with acid to release Ca2+ to induce mitochondrial damage and simultaneously produces O2 and H2O2, when the loaded MnO exerts Fenton-like activity to produce·OH and O2 based on the produced H2O2. The generated O2 drives Si-motor forward, thus endowing active delivery capability of the formed motors in TME. Meanwhile, MnO with glutathione (GSH) depletion ability further prevents reactive oxygen species (ROS) from being destroyed. Such TME actuated Si-motor with enhanced cellular uptake and deep penetration provides amplification of synergistic oxidative stresscausedbyintracellularCa2+overloading, GSH depletioninducedby Mn2+,andMn2+mediated chemodynamictreatment (CDT), leading to excellent tumor cell death. The created nanomotor may offer an effective platformfor active synergistic cancer treatment.

Flying‐Saucer‐Shaped Nanoheterojunctions with Enhanced Colorectal Tumor Accumulation for Increased Oxidative Stress and Immunometabolic Regulation

AbstractThe treatment outcomes of nanomedicines against colorectal cancer are severely restricted by their insufficient accumulation in the tumor tissues, unsatisfactory antitumor effect, and weak immunometabolic modulation. To address these issues, flying‐saucer‐shaped nanoheterojunctions by coating copper oxide (CuxO) onto the surface of PEGylated zinc oxide (ZnO) nanoparticles are constructed. When exposed to ultrasound, the resultant CuxO@ZnO nanoheterojunctions exhibit increased locomotor activities, facilitating colorectal mucus infiltration, deep tumor penetration, and tumor cell internalization. The decoration of CuxO suppresses the rapid recombination of electrons and holes in CuxO@ZnO exposed to ultrasound, promoting the production of singlet oxygen and hydroxyl radical, which are generated by CuxO through a Fenton‐like chemodynamic reaction and CuxO@ZnO through sonodynamic reaction. After rectal administration, the sono‐chemodynamic CuxO@ZnO plus PD‐L1 antibodies effectively inhibit the growth of orthotopic and distant tumors. It elicits immunometabolic responses by inducing immunogenic cell death, activating the interferon genes signaling pathway stimulator, and inhibiting glucose transport and the glycolytic signaling pathways. This combined modality also increases the proportion of beneficial microbes (e.g., Bifidobacterium) and decreases the abundance of harmful microorganisms (e.g., Romboutsia) in the intestine. This treatment modality (CuxO@ZnO plus ultrasound and PD‐L1 antibodies) is a promising strategy for the synergistic treatment of colorectal cancer.

Drug delivery particles for targeted imaging-guided photothermal/chemotherapy synergy cancer therapy

The early stage of pancreatic cancer is asymptomatic and the treatment effect is not ideal. The progression to the advanced stage leads to a close relationship between mortality and morbidity. Therefore, there is an urgent need to develop precise and efficient therapeutic strategies to combat pancreatic cancer. In this study, we introduce a near-infrared (NIR) targeted drug delivery nanoparticle for ultrasound (US) imaging to guide magnetothermal/chemotherapy synergistic treatment of pancreatic cancer. Carboxylated polylactic acid (PLGA-PEG-COOH) serves as the structure of the nanoparticles, specifically binding the RGD cyclic peptide for pancreatic cancer targeting activity and promoting tumor aggregation of the nanoparticles. NIR-induced superparamagnetic iron oxide (SPIO) nanoparticles convert near-infrared light into thermal energy, triggering vaporization of perfluoropentane (PFH) droplets to generate PFH bubbles that enhance US imaging and help load doxorubicin (DOX), which are released from nanoparticles. SPIO can also be used for thermal ablation of tumors to improve therapeutic effect in treating pancreatic cancer. The results show that the targeted particles mediated by NIR have the characteristics of targeted drug delivery imaging. The microspheres exhibit strong acoustic and near-infrared responsiveness. Cell proliferation experiments showed that IR-mediated PFH-DOX@PLGA/SPIO-RGD NPs (RNPs) had a higher inhibitory effect on cell proliferation. Animal experiments have shown that RNPS can accumulate highly in the tumor area and show good therapeutic effect. In conclusion, this nanotherapeutic particle is a very promising targeted image-guided photothermal/chemotherapeutic synergistic tumor therapy strategy.

Multifunctional calcium-based nanocarriers for synergistic treatment of triple-negative breast cancer

Targeted breast cancer therapies hold the potential to improve the efficiency of drug delivery to the pathology site without impacting the viability and function of healthy cells. Herein, we developed multifunctional nanocarriers that target simultaneously several downstream signaling processes in triple negative breast cancer cells. The system comprises pH sensitive CaCO3 nanoparticles (NPs) as carriers of the anticancer drug doxorubicin (DOX). The NPs were coated in a layer-by-layer (LbL) fashion using poly-l-lysine and hyaluronic acid to target receptors overexpressed in breast cancer (e.g. CD44, RHAMM). Spheroids of the triple-negative Hs578T cell line were used as a 3D model to assess the therapeutic potential of this system. Our results showed that the NPs act via a synergistic mechanism that combines Ca2+ overload causing cell calcification and DNA damage by DOX. The LbL coating was crucial for the protection of the healthy cells, i.e. it provides NPs with targeting capacity. The overall data suggests that the LbL-coated NPs loaded with DOX hold great potential for the treatment of breast cancer.