Chemo-photothermal Cancer Therapy Research Articles

Mesoporous polydopamine (MPDA)-based drug delivery system for oral chemo-photothermal combinational therapy of orthotopic colon cancer

Oral nano-drug delivery systems offering combination therapy have garnered significant interest in colon cancer treatment due to their precision in targeting tumors and minimizing peripheral tissue exposure. However, challenges such as the complex gastrointestinal environment and effective retention of nanoparticles in the colon have impeded further advancement. We developed a novel oral drug delivery system designed for localized treatment of colon cancer via chemotherapy and photothermal therapy (PTT). This system utilized mesoporous polydopamine (MPDA) as a photothermal carrier for doxorubicin hydrochloride (DOX), with surface modification using folic acid (FA) to enhance systemic tumor targeting. Additionally, to ensure gastrointestinal retention and precise colon localization, the nanoparticles were coated with an enteric-soluble material, ES100, resulting in the formulation MPDA-FA-DOX/ES100. This formulation exhibited high photothermal conversion efficiency, robust photothermal stability, and responsive drug release under near-infrared (NIR) laser stimulation. FA modification significantly enhanced the cellular uptake of nanoparticles by CT26 cells, promoting greater cytotoxic effects through combined chemotherapy and PTT. In vivo, MPDA-FA-DOX/ES100 demonstrated superior accumulation in colon tumor tissues and substantial photothermal effects, and notably, the CT/PTT group demonstrated significant tumor growth inhibition along with excellent biocompatibility. Collectively, these findings highlight the clinical potential of MPDA-FA-DOX/ES100 as an effective platform for localized and synergistic CT/PTT of colon cancer.

Docetaxel-Encapsulated Catalytic Pt/Au Nanotubes for Synergistic Chemo-Photothermal Therapy of Triple-Negative Breast Cancer.

The combination of photothermal therapy with chemotherapy has emerged as a promising therapeutic modality for addressing triple-negative breast cancer (TNBC). This manuscript describes a novel hybrid nanoplatform comprising ultrathin catalytic platinum/gold (Pt/Au) nanotubes encapsulated with docetaxel and phase-change materials (PCMs) for the photoacoustic imaging-guided synergistic chemo-photothermal therapy of TNBC. Upon irradiation of near-infrared laser, the photothermal heating of nanotubes converts solid-state PCM into liquid, triggering the controlled release of the encapsulated docetaxel. The thin Pt layer within nanotubes enhances the nanotube's thermal stability, thus prolonging the photothermal ablation of tumors. Furthermore, platinum effectively mitigates tumor hypoxia by catalyzing the decomposition of hydrogen peroxides to generate oxygen in the tumor microenvironment, thus improving the efficiency of chemotherapy. It is demonstrated that the drug-loaded nanotubes achieve significant tumor inhibition rates of 75.4% in vivo on 4T1 tumor-bearing mice, significantly surpassing control groups. These nanotubes also notably extend survival, attributable to the synergistic effects of prolonged photothermal therapy facilitated by platinum and oxygenation-enhanced chemotherapy. This combination leverages the unique properties of the Pt/Au NTs-DTX/PCM nanoplatform, optimizing therapeutic outcomes. It is envisioned that this nanoplatform may find important applications in managing superficial malignant solid tumors in general.

A targeting nanoplatform for chemo-photothermal synergistic therapy of small-cell lung cancer.

The precise delivery of drugs to tumor sites and the thermoresistance of tumors remain major challenges in photothermal therapy (PTT). Somatostatin receptor 2 (SSTR2) is proposed as an ideal target for the precise treatment of SCLC. We developed a targeting nano-drug delivery system comprising anti-SSTR2 monoclonal antibody (MAb) surface-modified nanoparticles co-encapsulating Cypate and gambogic acid (GA). The formed SGCPNs demonstrated excellent monodispersity, physiological stability, preferable biocompatibility, and resultant efficient photothermal conversion efficacy. SGCPNs were quickly internalized by SSTR2-overexpressing SCLC cells, triggering the release of GA under acidic and near-infrared (NIR) laser irradiation environments, leading to their escape from lysosomes to the cytosol and then diffusion into the nucleus. SGCPNs can not only decrease the cell survival rate but also inhibit the activity of heat shock protein 90 (HSP90). SGCPNs can be precisely delivered to xenograft tumors of SSTR2-positive SCLC in vivo. Upon NIR laser irradiation, therapy of SGCPNs showed significant tumor regression. In conclusion, SGCPNs provide a new chemo-photothermal synergistic treatment strategy for targeting SCLC.

Laser-activable murine ferritin nanocage for chemo-photothermal therapy of colorectal cancer

Chemotherapy, as a conventional strategy for tumor therapy, often leads to unsatisfied therapeutic effect due to the multi-drug resistance and the serious side effects. Herein, we genetically engineered a thermal-responsive murine Ferritin (mHFn) to specifically deliver mitoxantrone (MTO, a chemotherapeutic and photothermal agent) to tumor tissue for the chemotherapy and photothermal combined therapy of colorectal cancer, thanks to the high affinity of mHFn to transferrin receptor that highly expressed on tumor cells. The thermal-sensitive channels on mHFn allowed the effective encapsulation of MTO in vitro and the laser-controlled release of MTO in vivo. Upon irradiation with a 660 nm laser, the raised temperature triggered the opening of the thermal-sensitive channel in mHFn nanocage, resulting in the controlled and rapid release of MTO. Consequently, a significant amount of reactive oxygen species was generated, causing mitochondrial collapse and tumor cell death. The photothermal-sensitive controlled release, low systemic cytotoxicity, and excellent synergistic tumor eradication ability in vivo made mHFn@MTO a promising candidate for chemo-photothermal combination therapy against colorectal cancer.Graphical

Self-assembled IR dye/mitoxantrone loaded Porphysomes nanosystem for enhanced combinatorial chemo-photothermal cancer therapy

Chemo-photothermal therapy (PTT) is an emerging non-invasive cancer treatment modality. Light-responsive porphysomes (DPP IR Mtx @Lipo NPs) nanosystems ablate breast cancer cells upon oxidative stress and hyperthermia. The unique self-assembled porphysomes were formed spherical shape in the size range of 150 ± 30 nm formed by the co-assembly of porphyrins along with IR 775 and chemotherapeutic drug, Mitoxantrone (Mtx), forming a camouflaged nanosystem (DPP IR Mtx @Lipo NPs, porphysomes). The advent of the prepared porphysomes aids in proper tuning of NIR absorbance improving singlet oxygen species generation among other anticancer drugs. The eminent release of DPP and adjuvant chemo-drug, Mitoxantrone from the self-assembled porphysomes is triggered by IR 775, a NIR photosensitizer upon laser irradiation. These multifunctional DPP IR Mtx @Lipo NPs have an efficient photothermal conversion efficiency of 65.8% as well as bioimaging properties. In-vitro studies in 2D and 3D models showed a significant cell death of 4T1 cells via the apoptotic pathway when irradiated with NIR laser, causing minimal damage to nearby healthy cells. DPP IR Mtx @Lipo NPs exhibited commingled PDT/PTT interdependent via NIR laser exposure, leading to mitochondrial disruption. Interestingly, the transient transfection using p53-GFP in cancer cells followed by DPP IR Mtx @Lipo NPs treatment causes rapid cell death. The activation of p53-dependent apoptosis pathways was vividly expressed, evidenced by the upregulation of Bax and increased pattern of Caspase-3 cleavage. This effect was pronounced upon transfection and induction with DPP IR Mtx @Lipo NPs, particularly in comparison to non-transfected malignant breast cancer 4T1 cells.

Propolis polyphenol nanosheet for synergistic cancer chemo-photothermal therapy

Two-dimensional (2D) carbon-based nanostructures hold great promise as near-infrared (NIR) photothermal materials, yet their widespread use has been hindered by labor-intensive and costly fabrication processes. Here, a novel, cost-effective approach is presented to produce photothermal materials derived from the polyphenolic fraction of propolis (PFP) for the first time. The method involves the pyrolysis of PFP under a neutral atmosphere, resulting in the formation of 2D PFP-based nanosheets (PFPNS) measuring 50–100 nm in size with efficient photothermal properties. Then, a layer-by-layer nanohybrid structure comprising PFPNS, polydopamine (PDA), mesoporous silica (MS), and polyethyleneimine (PEI) layers (PFPNS@PDA@MS-PEI) was designed as a versatile platform for drug delivery. Specifically, the anticancer drug doxorubicin (DOX) was loaded onto the nanohybrid (PFPNS@PDA@MS(DOX)-PEI) for targeted delivery to cancerous cells. Each layer of the nanohybrid serves a distinct purpose, enhancing functionality and efficacy. The NIR-responsive PFPNS@PDA component facilitates accelerated drug release and induces hyperthermic effects on cancer cells upon NIR irradiation. The MS structure enables high drug loading capacity (approximately 83.3%), while the pH-responsive PEI layer promotes cellular uptake and facilitates drug release within the acidic microenvironment of cancer cells. Combining NIR irradiation with chemotherapy results in a synergistic effect, leading to the eradication of 67% of MCF-7 breast cancer cells. The demonstrated efficacy, coupled with the non-toxic nature of the nanohybrid, positions it as a promising candidate for synergistic chemo-photothermal therapy of tumor tissues.

The collaborated assembly of hydrophobic curcumin and hydrophilic cyanine dye into nanocolloid for synergistic chemo-photothermal cancer therapy

Carrier-free nanomedicine represents a new opportunity of using less inert materials for efficient drug delivery. To date, most reported carrier-free nanomedicine systems rely heavily on π-π stacking interaction between hydrophobic drugs. This work found that the hydrophilic IR783 dye can collaborate with the hydrophobic curcumin (Cur) compound to form a novel Cur@IR783 nanocolloid (NC) via self-assembly. The self-assembly of the hydrophilic IR783 and hydrophobic Cur improved the water dispersity of Cur, significantly facilitating its administration in vivo. Moreover, Cur@IR783 NC retained the IR783 properties of NIR fluorescence and photothermal conversion efficiency. Fluorescence imaging demonstrated that Cur@IR783 NC accumulated at the tumor site via the enhanced permeation and retention effect, which ensured enhanced anti-tumor effect. In vitro and in vivo experiments showed that the Cur@IR783 NC with laser irradiation yielded the most potent antitumor effect, and Cur@IR783 NC exhibited high biocompatibility. Overall, Cur@IR783 NC showed remarkable synergistic antitumor activity via chemo-photothermal combination therapy, providing a new promising approach for Cur-based applications in cancer treatment.

Polydopamine nanoplatform with near infrared light and pH dual stimuli-responsive for chemo-photothermal cancer therapy.

Photothermal agent accompanying with thermally responsive materials, displays well controlled drug release property, which is well-received as an outstanding design strategy for simultaneous photothermal/chemotherapy in cancer. Cyanine dye, as the prestigious photothermal agent has shown great potential due to its preeminent near-infrared absorbance and excellent thermal conversion efficiency. However, their inherent defect such as inferior photothermal stability, high leakage risk and poor therapy efficacy limit their further application in cancer therapy. Hence, a facile and universal strategy to make up these deficiencies is developed. Chemotherapeutic drug DOX and cyanine dye were loaded into polydopamine (PDA) nanoparticles. The PDA encapsulation dramatically improved the photothermal stability of cyanine dye. Attributed by the PDA structure feature, the thermo-sensitive small molecule glyamine (Gla) is introduced into the PDA surface to lessen leakage. The Gla can form a dense encapsulation layer on the dopamine surface through hydrogen bond. This newly fabricated Cyanine/DOX@PDA-Gla nanopaltform is characterized with NIR light/pH dual-responsive property, high NIR photothermal conversion performance and fluorescence guided chemo-photothermal therapy.

Synergistic Chemo-Photothermal Therapy of Breast Cancer Based on Mesoporous Polydopamine Nanoparticles Decorated with Atovaquone

Synergistic Chemo-Photothermal Therapy of Breast Cancer Based on Mesoporous Polydopamine Nanoparticles Decorated with Atovaquone

Cancer Cell Membrane-Biomimetic Nanoparticles Based on Gelatin and Mitoxantrone for Synergetic Chemo-Photothermal Therapy of Metastatic Breast Cancer.

The purpose of this paper is to develop a cancer cell membrane biomimetic nanodrug delivery system (NDDS) to achieve an enhanced chemo-photothermal synergistic antitumor effect. The biomimetic NDDSs are composed of mitoxantrone (MIT)-loaded gelatin nanoparticles and IR820-encapsulated 4T1 cancer cell membrane-derived vesicles. The biomimetic NDDS displayed excellent stability and photothermal conversion efficiency. Compared to naked nanoparticles, the cell membrane-coated nanoparticles improved 4T1 cell uptake through homologous targeting and effectively reduced internalization of macrophages. In vivo photothermal imaging results further showed that the NDDS could be enriched at the tumor site for 48 h and could raise the temperature of the tumor area to 60 °C within 5 min under 808 nm laser irradiation. Finally, NDDS successfully inhibited primary tumor growth (over 89% inhibition) and significantly inhibited lung metastasis. This study may provide a new strategy for personalized chemotherapy-photothermal combination therapy of metastatic breast cancer using tumor cell membranes from cancer patients as drug carriers.

Fabrication and characterization smart gold-polymer nanostructure as promising theranostic agent for dual-imaging and chemo-photothermal therapy of cancer: An in vitro study

In order to enhance the effectiveness of cancer therapy, it is essential to have highly sensitive imaging techniques that provide accurate results and the selection of appropriate therapeutic strategies. Despite recent advances in technologies associated with tumor imaging, the application of conventional single-mode imaging is the subject of debate. Herein, we strategically engineered a nanostructure (GNSs-MTX@CD-Pol) designed from a pH-responsive polymer (Pol), gold nanostar (GNSs), carbon dot (CD), and methotrexate (MTX) as a theranostic agent for simultaneously fluorescent (FI) and X-ray computed tomography (CT) imaging and combination Chemo-Photothermal Therapy in response to near-infrared (NIR) laser irradiation. GNSs-MTX@CD-Pol NPs possess excellent photothermal conversion efficiency and dual FI/CT imaging properties, which are attributed to the strong NIR absorption and high atomic number of gold elements. Moreover, it is demonstrated that GNSs-MTX@CD-Pol NPs are effectively responding to tumor acidity. With the PTT, the growth of cancer cells can be remarkably ablated in vitro. The results of the cell cycle, apoptosis, real-time PCR, and western blotting test on MDA-MB-231 cells revealed antitumor effect of GNSs-MTX@CD-Pol NPs caused by combination Chemo-Photothermal Therapy. Based on their high stability and excellent biocompatibility, GNSs-MTX@CD-Pol NPs have great potential for the treatment of various types of tumors.

Hyaluronic acid-functionalized graphene-based nanohybrids for targeted breast cancer chemo-photothermal therapy

Nanomaterials’ application in cancer therapy has been driven by their ability to encapsulate chemotherapeutic drugs as well as to reach the tumor site. Nevertheless, nanomedicines’ translation has been limited due to their lack of specificity towards cancer cells. Although the nanomaterials’ surface can be coated with targeting ligands, such has been mostly achieved through non-covalent functionalization strategies that are prone to premature detachment. Notwithstanding, cancer cells often establish resistance mechanisms that impair the effect of the loaded drugs. This bottleneck may be addressed by using near-infrared (NIR)-light responsive nanomaterials. The NIR-light triggered hyperthermic effect generated by these nanomaterials can cause irreversible damage to cancer cells or sensitize them to chemotherapeutics’ action. Herein, a novel covalently functionalized targeted NIR-absorbing nanomaterial for cancer chemo-photothermal therapy was developed. For such, dopamine-reduced graphene oxide nanomaterials were covalently bonded with hyaluronic acid, and then loaded with doxorubicin (DOX/HA-DOPA-rGO). The produced nanomaterials showed suitable physicochemical properties, high encapsulation efficiency, and photothermal capacity. The in vitro studies revealed that the nanomaterials are cytocompatible and that display an improved uptake by the CD44-overexpressing breast cancer cells. Importantly, the combination of DOX/HA-DOPA-rGO with NIR light reduced breast cancer cells’ viability to just 23 %, showcasing their potential chemo-photothermal therapy.

Bufotalin-loaded biomimetic Prussian blue nanoparticles for colorectal cancer chemo-photothermal ferroptosis therapy.

Purpose: We constructed biomimetic nanoparticles with biocompatible, tumor-targeting, laser-responsive properties for ferroptosis-induced colorectal cancer chemo-photothermal therapy, with the aim to realize double-hit ferroptosis treatment for colorectal cancer. Methods: The nanoparticles were prepared by first loading the chemotherapy drug bufotalin (CS-5) with Prussian blue (PB), then combining a hybridized erythrocyte-tumor membrane (M) with PB@CS-5 to produce PB@CS-5@M. The chemo-photothermal therapy efficiency of PB@CS-5@M was tested by in vitro and in vivo experiments. Results and conclusion: The combined PB and CS-5 act as promising ferroptosis inducers to enhance ferroptosis efficacy. The hyperthermia induced by laser stimulation can trigger PB to release CS-5 and iron and ferrous ions, which further promotes ferroptosis.

Double-shelled, rattle-architecture covalent organic framework: harnessing morphological manipulation for enhanced synergistic multi-drug chemo-photothermal cancer therapy.

Morphological modulation in covalent organic frameworks (COFs) with particular emphasis on the correlation between structure and target applications in biomedical fields, is currently in its early stage of evolution. Herein, a multifunctional rattle-architecture imine-based COF with a mobile core of gold nanoparticles (Au NPs) and an outer polydopamine (PDA) shell, tailored for cancer treatment, has been developed to effectively integrate dual responsive release capabilities with the potential for multiple therapeutic applications. The engineered COF displays outstanding crystallinity, a suitable size and precisely controlled morphological characteristics. By leveraging COF and PDA attributes, the successful co-delivery of hydrophilic doxorubicin (DOX) and hydrophobic docetaxel (DTX) within discrete compartments is achieved responsive to both pH and near-infrared triggers. Designed nanocarrier outperforms prior COFs with a superior 83.7% DOX loading capacity, thanks to its expansive internal space and porous shell. Taking advantage of the inclusion of Au core and the concurrent presence of COF and PDA outer shells, the nanocarrier exhibits a significant photothermal-conversion capability. The rattle-architecture double-shelled Au@RCOF@PDA were functionalized with poly(ethylene glycol)-folic acid (PEG-FA) to confer the system with active-targeting capability and enhanced biocompatibility. Through in vitro and in vivo evaluations, the designed system demonstrates an exceptional synergistic anti-tumor effect, along with favorable biosafety and histocompatibility. This study not only sheds light on the remarkable merits offered by regulating the morphology of COF-based systems in cancer therapy but also highlights the potential for synergistic therapeutic approaches in advancing cancer treatment strategies.

Polydopamine modified by pillar[5]arene in situ for targeted chemo-photothermal cancer therapy.

A pillar[5]arene-modified polydopamine (PDA-P[5]OH) displaying pH/NIR dual-responsive properties was constructed successfully in situ for targeted chemo-photothermal cancer therapy.

Fabrication of BiCuOS nanoflowers acting as nanoarrays on photonic nanoparticles for chemo-photothermal therapy

In recent years, 3D flower shaped nanostructures with an ability to improve internal photo reflections and absorptions is gaining popularity for the development of photo-thermal heat generating materials for cancer therapy. The use of bimetallic oxysulfide materials as photo-thermal agent is especially interesting as it is not only resulting in heat generation by absorbing laser light in the biological window but also participates in reactive oxygen species generation in tumor environment. In this work, we have reported a novel flower shaped BiCuOS nanostructures made of CuS base structures with vertical nanoarrays of bismuth oxide nanoplates for synergistic chemo-photothermal cancer therapy. Notably, 2D nanoplates (∼150 ± 50 nm in length and thickness of about ∼25 nm) could be seen grown in the form of nanoflowers (NFs) of 800 ± 100 nm in size on CuS base structures. The electronic structure, density of states, bond angle, bond length and thermal stability of formed NFs were investigated by density functional theory and molecular dynamic studies. The photo-thermal conversion efficiency was increased as a function of NF concentration. The percentage of doxorubicin released was estimated to be only ∼4% even after one day of incubation at pH 7.4 which increased to 38 and 45% at pH 5.5 without and with near infra-red light exposure, respectively. The cell viability experiments with fibroblast cells and red blood cells exhibited excellent biocompatibility of BiCuOS NFs. The synthesized BiCuOS NFs showed excellent anticancer activity against Hep-2 cells. Hence, the BiCuOS NFs reported here have huge potential for use as novel dual performing chemo-and-photothermal agent for advanced cancer therapy.

Nanozyme controlled photothermal heat generation on nanoceria decorated MoS2 nanoflowers for enhanced cytotoxicity in cancer chemo-photothermal therapy

In recent years, the fabrication of nanomaterials with built-in ability to mimick biological enzymes (nanozymes) is gaining popularity for biomedical applications, especially for cancer photothermal therapy, based on non-toxic and photo-thermal heat generating 2D materials. The use of 2D inter-layered MoS2 nanoflowers (NFs) is especially interesting as it results in nanozymes that are photostable and biocompatible for normal cells under physiological conditions. In this work, we have synthesized MoS2 nanoflowers (NFs) decorated with CeO2 nanoparticles (NPs) using two linker molecules of cysteine and polyethylenimine connected through carbodiimide chemistry. The electron microscopy investigations revealed the formation of flower shaped MoS2 of 400 ± 100 nm in size decorated with spherical shaped CeO2 NPs of 15±5 nm in size. The fabricated nanozymes were investigated by UV–visible (UV–vis), FTIR spectroscopy, Raman spectroscopy and dynamic light scattering. The NFs decorated with long-chain PEI molecules demonstrated higher photo-thermal heat generation when compared to nanozymes decorated with low molecular weight PEI. Notably, the photo-thermal heat generation, biocompatibility, anti-cancer activity of nanozymes are significantly influenced by molecular weight of PEI, concentration of nanozymes, time duration of near-infrared (NIR) light exposure, power density of NIR light and folic acid (FA) conjugation. The nanozymes conjugated with FA on their surface exhibited excellent anti-cancer activity against human colon cancer cells under NIR light exposure at 808 nm and 0.5 W/cm2. Hence, the nanozymes demonstrated here have huge potential as nanophoto-thermal agents in cancer photothermal therapy.

Tumor-derived covalent organic framework nanozymes for targeted chemo-photothermal combination therapy

Covalent organic frameworks (COFs) have garnered enormous attention in anti-cancer therapy recently. However, the intrinsic drawbacks such as poor biocompatibility and low target-specificity greatly restrain the full clinical implementation of COF. Herein, we report a biomimetic multifunctional COF nanozyme, which consists of AIEgen-based COF (TPE-s COF) with encapsulated gold nanoparticles (Au NPs). The nanozyme was co-cultured with HepG2 cells until the cell membrane was fused with lipophilic TPE-s COF-Au@Cisplatin. By using the cryo-shocking method, we fabricated an inactivated form of the TPE-s COF-Au@Cisplatin nanozyme endocytosed in the HepG2 cell membrane (M@TPE-s COF-Au@Cisplatin), which lost their proliferative ability and pathogenicity. Upon laser irradiation, the M@TPE-s COF-Au@Cisplatin nanozymes cleaved, thereby releasing the TPE-s COF-Au nanozyme and Cisplatin to exert their photothermal and drug therapeutic effect. This work opens a new avenue to the synthesis of tumor-derived fluorescent TPE-s COF-Au nanozymes for highly efficient, synergetic, and targeted chemo-photothermal combination therapy of liver cancer.

AS1411-conjugated doxorubicin-loaded silver nanotriangles for targeted chemo-photothermal therapy of breast cancer.

Background: Combination therapy has attracted tremendous interest for its great potential in treating cancers. Materials & methods: Based on chitosan-coated silver nanotriangles, polyethylene glycol, AS1411 aptamer and doxorubicin, a multifunctional nanocomposite (AS1411-DOX-AgNTs) was constructed and characterized. Then the photothermal properties, ability to target breast cancer cells and anti-breast cancer effect of AS1411-DOX-AgNTs were evaluated. Results: AS1411-DOX-AgNTs were successfully fabricated andshowed excellent photothermal conversion efficiency, breast cancer cell and tumor targeting ability. Compared with single treatments, the combination of AS1411-DOX-AgNTs with near-infrared irradiation possessed the strongest anti-breast cancer effect in vitro and in vivo. Conclusion: AS1411-DOX-AgNTs hold great potential in targeted DOX delivery and combined chemo-photothermal therapy for breast cancer.

Hollow carbon nanospheres loaded with upconversion nanoparticles for chemo-photothermal synergistic cancer therapy

Hollow carbon nanospheres loaded with upconversion nanoparticles for chemo-photothermal synergistic cancer therapy