Chemo-photothermal Combination Therapy Research Articles

Acid-Activated TAT Peptide-Modified Biomimetic Boron Nitride Nanoparticles for Enhanced Targeted Codelivery of Doxorubicin and Indocyanine Green: A Synergistic Cancer Photothermal and Chemotherapeutic Approach.

The evolution of nano-drug delivery systems addresses the limitations of conventional cancer treatments with stimulus-responsive nanomaterial-based delivery systems presenting temporal and spatial advantages. Among various nanomaterials, boron nitride nanoparticles (BNNs) demonstrate significant potential in drug delivery and cancer treatment, providing a high drug loading capacity, multifunctionality, and low toxicity. However, the challenge lies in augmenting nanomaterial accumulation exclusively within tumors while preserving healthy tissues. To address this, we introduce a novel approach involving cancer cell membrane-functionalized BNNs (CM-BIDdT) for the codelivery of doxorubicin (Dox) and indocyanine green to treat homologous tumor. The cancer cell membrane biomimetic CM-BIDdT nanoparticles possess highly efficient homologous targeting capabilities toward tumor cells. The surface modification with acylated TAT peptides (dTAT) further enhances the nanoparticle intracellular accumulation. Consequently, CM-BIDdT nanoparticles, responsive to the acidic tumor microenvironment, hydrolyze amide bonds, activate the transmembrane penetrating function, and achieve precise targeting with substantial accumulation at the tumor site. Additionally, the photothermal effect of CM-BIDdT under laser irradiation not only kills cells through thermal ablation but also destroys the membrane on the surface of the nanoparticles, facilitating Dox release. Therefore, the fabricated CM-BIDdT nanoparticles orchestrate chemo-photothermal combination therapy and effectively inhibit tumor growth with minimal adverse effects, holding promise as a new modality for synergistic cancer treatment.

Polydopamine-Modified Copper Coordination Mesoporous Silica Nanoparticles Loaded with Disulfiram for Synergistic Chemo-Photothermal Therapy.

Disulfiram (DSF) degrades to diethyldithiocarbamate (DTC) in vivo and coordinates with copper ions to form CuET, which has higher antitumor activity. In this study, DSF@CuMSN-PDA nanoparticles were prepared using mesoporous silica with copper ions, DSF as a carrier, and polydopamine (PDA) as a gate system. The nanoparticles selectively released CuET into tumor tissue by taking advantage of the tumor microenvironment, where PDA could be degraded. The release ratio reached 79.17% at pH 5.0, indicating pH-responsive drug release from the nanoparticles. The PDA-gated system provided the nanoparticles with unique photothermal conversion performance and significantly improved antitumor efficiency. In vivo, antitumor experiments showed that the designed DSF@CuMSN-PDA nanoparticles combined with near-infrared light (808 nm, 1 W/cm2) irradiation effectively inhibited tumor growth in HCT116 cells by harnessing the combined potential of chemotherapy and photothermal therapy; a synergistic effect was achieved. Taken together, these results suggest that the designed DSF@CuMSN-PDA construct can be employed as a promising candidate for combined chemo-photothermal therapy.

Plasmonic laser-responsive BioDissolve 3D-printed graphene@cisplatin-implant for prevention of post-surgical relapse of oral cancer

The development of chemoresistance is a major obstacle in post-surgical adjuvant therapy of cancer, leading to cancer cell survival, recurrence, and metastasis. This study reports a 3D-printed plasmonic implant developed for the post-surgical adjuvant therapy of cisplatin-resistant cancer cells to prevent relapse. The implant was printed using optimized biomaterial ink containing biodegradable polymers [poly(L-lactide) and hydroxypropyl methylcellulose] blended suitably with laser-responsive graphene and chemo drug (Cisplatin). The irradiation of scar-driven 3D-printed implant with a laser stimulates graphene to generate a series of hyperthermia events leading to photothermolysis of cisplatin-resistant cancer cells under the combined influence of sustained cisplatin release. The developed personalized implant offers pH-responsive sustained drug release for 28 days. The implant exhibited acceptable biophysical properties (Tensile strength: 3.99 ± 0.15 MPa; modulus: 81 ± 9.58 MPa; thickness: 110 μm). The 3D-printed implant effectively reverses the chemoresistance in cisplatin-resistant 3D spheroid tumor models. Cytotoxicity assay performed using cisplatin-resistant (CisR) cell line revealed that the cell viability was reduced to 39.80 ± 0.68 % from 61.37 ± 0.98 % in CisR tumor spheroids on combined chemo-photothermal therapy. The combination therapy reduced the IC50 value from 71.05 μM to 48.73 μM in CisR spheroids. Apoptosis assay revealed an increase in the population of apoptotic cells (35.45 ± 1.56 % →52.53 ± 2.30 %) on combination therapy. A similar trend was observed in gene expression analysis, where the expression of pro-apoptotic genes Caspase 3 (3.73 ± 0.04 fold) and Bcl-2-associated X protein (BAX) (3.35 ± 0.02 fold) was increased on combination therapy. This 3D-printed, biodegradable implant with chemo-combined thermal ablating potential may provide a promising approach for the adjuvant treatment of resistant cancer.

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.

Bilayered porous composite scaffolds for enhanced treatment of bone cancer through chemo-photothermal combination therapy

Bilayered porous composite scaffolds for enhanced treatment of bone cancer through chemo-photothermal combination therapy

Synergistic chemo-photothermal therapy using gold nanorods supported on thiol-functionalized mesoporous silica for lung cancer treatment

Cancer therapy necessitates the development of novel and effective treatment modalities to combat the complexity of this disease. In this project, we propose a synergistic approach by combining chemo-photothermal treatment using gold nanorods (AuNRs) supported on thiol-functionalized mesoporous silica, offering a promising solution for enhanced lung cancer therapy. To begin, mesoporous MCM-41 was synthesized using a surfactant-templated sol–gel method, chosen for its desirable porous structure, excellent biocompatibility, and non-toxic properties. Further, thiol-functionalized MCM-41 was achieved through a simple grafting process, enabling the subsequent synthesis of AuNRs supported on thiol-functionalized MCM-41 (AuNR@S-MCM-41) via a gold-thiol interaction. The nanocomposite was then loaded with the anticancer drug doxorubicin (DOX), resulting in AuNR@S-MCM-41-DOX. Remarkably, the nanocomposite exhibited pH/NIR dual-responsive drug release behaviors, facilitating targeted drug delivery. In addition, it demonstrated exceptional biocompatibility and efficient internalization into A549 lung cancer cells. Notably, the combined photothermal-chemo therapy by AuNR@S-MCM-41-DOX exhibited superior efficacy in killing cancer cells compared to single chemo- or photothermal therapies. This study showcases the potential of the AuNR@S-MCM-41-DOX nanocomposite as a promising candidate for combined chemo-photothermal therapy in lung cancer treatment. The innovative integration of gold nanorods, thiol-functionalized mesoporous silica, and pH/NIR dual-responsive drug release provides a comprehensive and effective therapeutic approach for improved outcomes in lung cancer therapy. Future advancements based on this strategy hold promise for addressing the challenges posed by cancer and transforming patient care.

Dual-functional nano-carrier system based on NIR-laser-triggered dynamic Au[sbnd]Se interaction for chemo-photothermal synergistic tumor therapy

Photothermal therapy (PTT) combined with chemotherapy has been highly desirable to improve the tumor treatment efficacy. Here, we report a novel controlled release nano-carrier system named Se-PEG-Au NPs-DOX (SePAD) for achieving chemo-photothermal synergistic tumor therapy. In this system, the diselenide-containing co-polymers (mPEG-Se–Se-PEGm) were anchored onto the surface of Au NPs via AuSe interactions and the soluble chemotherapeutic doxorubicin (Dox) was loaded into the monolayers. This structure is proved to be stable in a high biological thiols environment. Strikingly, the SePAD presents an ideal efficient photothermal capability and a controllable Dox release behavior by dynamic AuSe interaction in GSH-rich tumor cells when irradiated under 808 nm NIR laser. Following, the results of in vitro and in vivo experiments all demonstrat the superior antitumor properties of SePAD in murine breast cancer. Thus, this system provides a promising strategy to realize chemo-photothermal synergistic combination therapy for breast tumors.

Preparation of GSH-responsive nanoparticles for combined chemo-photothermal therapy codelivering 6-MP and Ce6

A glutathione (GSH)-responsive nano-drug delivery system combining photodynamic therapy (PDT) and chemotherapy (CT) was developed for lymphoma. The small-molecule reduction-sensitive 6-mercaptopurine (PTA) and photosensitizer chlorine6 (Ce6) were loaded onto carboxymethyl chitosan (CMCS), a biocompatible and water-soluble carrier. Through ultrasonic self-assembly, dual drug combination nanoparticles (CCP NPs) with an average particle size of 169 ± 1.9 nm in the water have been developed. PTA is sensitive to GSH and degrades quickly in tumor cells with high GSH levels, which causes the disintegration of nanoparticles and the release of 6-mercaptopurine (6-MP). Immediately thereafter, the Ce6 embedded in the nanoparticles was released to achieve sequential drug release. The PTA structure's Michael receptor significantly reduces GSH levels in tumor cells, which diminishes GSH's antioxidant influence on photosensitizers' ability to produce reactive oxygen species (ROS) and enhances PDT in a synergistic way. The CCP NPs revealed a nanometric size distribution, optimal surface charge and excellent stability. An in vitro toxicity study revealed that 6-MP and Ce6 exhibited strong selectivity (SI = 4.23) and a synergistic impact (CI = 0.23) on Black Burkitt's lymphoma cells (Raji cells). Research on drug delivery systems that combine Ce6 and 6-MP is a valuable new strategy for lymphoma.

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.

3D-printed NIR-responsive bullets as multifunctional nanodrug platforms for image-guided local chemo-photothermal therapy

Multimodal cancer treatment that combines anticancer drug delivery with other therapeutic strategies, such as photothermal therapy, has shown enormous potential for biomedical applications. However, traditional nanoscale photothermal conversion agents require complicated synthesis processes and lack biosafety, detectability, and mechanical reinforcement ability in the hyperthermia platform. Here, we engineered near-infrared laser (NIR)-responsive bullets as multifunctional nanodrug platforms via a three-dimensional (3D) printing process as an image-guided versatile chemo-photothermal cancer treatment platform. This customizable platform not only serves as a container for anticancer nanodrugs but also possesses excellent radiopacity and high photothermal conversion efficiency, merging on-demand anticancer nanodrug release and hyperthermia effect. Benefiting from the combined chemo-photothermal therapy, the 3D-printed platform showed enhanced cytotoxicity to cancer cells in vitro. Furthermore, in vivo results confirmed effective on-demand nanodrug release and synergistic inhibition of tumor growth upon NIR laser irradiation. 3D-printed NIR-responsive bullets can synergistically enhance anticancer efficiency while evading potential clinical application risks, offering great potential for multimodal cancer therapies.

Functionalized N-hydroxypropyl trimethylammonium chloride chitosan as an ICG/DOX co-delivery nanocarriers for targeted and chemo-photothermal combination therapy

Functionalized N-hydroxypropyl trimethylammonium chloride chitosan as an ICG/DOX co-delivery nanocarriers for targeted and chemo-photothermal combination therapy

Cubosomes-assisted transdermal delivery of doxorubicin and indocyanine green for chemo-photothermal combination therapy of melanoma

Melanoma is a highly aggressive form of skin cancer with limited therapeutic options. Chemo-photothermal combination therapy has demonstrated potential for effectively treating melanoma, and transdermal administration is considered the optimal route for treating skin diseases due to its ability to bypass first-pass metabolism and enhance drug concentration. However, the stratum corneum presents a formidable challenge as a significant barrier to drug penetration in transdermal drug delivery. Lipid-nanocarriers, particularly cubosomes, have been demonstrated to possess significant potential in augmenting drug permeation across the stratum corneum. Herein, cubosomes co-loaded with doxorubicin (DOX, a chemotherapeutic drug) and indocyanine green (ICG, a photothermal agent) (DOX-ICG-cubo) transdermal drug delivery system was developed to enhance the therapeutic efficiency of melanoma by improving drug permeation. The DOX-ICG-cubo showed high encapsulation efficiency of both DOX and ICG, and exhibited good stability under physiological conditions. In addition, the unique cubic structure of the DOX-ICG-cubo was confirmed through transmission electron microscopy (TEM) images, polarizing microscopy, and small angle X-ray scattering (SAXS). The DOX-ICG-cubo presented high photothermal conversion efficiency, as well as pH and thermo-responsive DOX release. Notably, the DOX-ICG-cubo exhibited enhanced drug permeation efficiency, good biocompatibility, and improved in vivo anti-melanoma efficacy through the synergistic effects of chemo-photothermal therapy. In conclusion, DOX-ICG-cubo presented a promising strategy for melanoma treatment.

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.

Development and characterization of pH-responsive nanocarriers for chemo-photothermal combination therapy of acidic tumors.

The combination of photothermal therapy and chemotherapy has been considered a promising strategy for improving the excellent antitumor activities of these treatments. In this study, we developed a new simple type of pH-sensitive chemo-photothermal combination agent capable of repeated exposures to a near-infrared (NIR) laser and evaluated its anticancer efficacy in vitro and in vivo. Doxorubicin (Dox) and gold nanoclusters (GNCs) were successfully co-loaded into pH-sensitive nanoparticles (poly(ethylene glycol)-poly[(benzyl-l-aspartate)-co-(N-(3-aminopropyl)imidazole-L-aspartamide)] (PEG-PABI)), resulting in a particle size of approximately120 nm with a narrow size distribution. The dual drug-loaded nanoparticles (Dox/GNC-loaded PEG-PABI micelles (Dox/GNC-Ms)) showed consistent pH-sensitive properties and heat generation efficiency after repeated NIR laser exposure. In particular, GNC-M has improved photothermal stability while maintaining high photothermal conversion efficiency, addressing the shortcomings of previous gold nanoparticles. As the concentration of GNC-Ms, irradiation light exposure time, and light source intensity increased, the amount of heat generated and the anticancer effect increased. When Dox was encapsulated with GNCs (Dox/GNC-Ms), a faster drug release rate under acidic pH conditions and a strong synergistic effect against U87MG cells were observed. When the Dox/GNC-M system was extended to in vivo studies, it effectively increased the temperature of the tumor tissue under near-infrared irradiation and showed excellent anticancer efficacy. Therefore, the Dox/GNC-M system could be a simple but promising strategy for chemo-photothermal combination treatment capable of targeting acidic tumors.

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.

Acid-responsive DNA-Au nanomachine with active/passive dual-targeting capacity for combinational cancer therapy

DNA nanotechnology has attracted intense interest in biomedicine due to the advantages of good biocompatibility, structural programmability and multifunctionality. Herein, a DNA-Au nanomachine with active/passive dual-targeting capacity has been constructed, achieving lysosomal acidic microenvironment-activated combinational chemo-photothermal therapy of cervical carcinoma. The three-dimensional DNA nanoflowers (DNFs) are readily prepared via rolling circle amplification (RCA), in which the active targeting units (C-9S aptamers) for HeLa cells and drug-loading sites for doxorubicin (Dox) are rationally designed in the circular template. Meanwhile, the bovine serum albumin (BSA)-modified gold nanoparticles (BSA-AuNPs) with pH-responsive charge reversal ability are internalized into cancer cells through passive targeting mechanism of enhanced permeability and retention (EPR) effect. Under acidic stimuli (endosome and lysosome), the loaded Dox in DNFs is controllably released for targeted chemotherapy, and the charge of BSA-AuNPs is reversed from negative to positive in lysosome, resulting in the aggregation of BSA-AuNPs on DNFs through electrostatic interaction. Thus, hyperthermia is produced upon 808 nm laser irradiation for photothermal therapy (PTT). The in vitro and in vivo results demonstrate the highly chemo-photothermal therapy effect on cervical cancer based on the proposed DNA-Au nanomachine, providing a powerful and potential nanotheranostic platform for targeted combinational therapy of cancers in clinical applications.

An inorganic-organic-polymeric nanovehicle for targeting delivery of doxorubicin: Rational assembly, pH-stimulus release, and dual hyperthermia/chemotherapy of hepatocellular carcinoma.

Efficiently synergistic therapy of hepatocellular carcinoma (HCC) by chemotherapeutic drug and photothermal agent remains a considerable challenge. Here, we report a nanodrug that integrates specific hepatoma-targeted delivery, pH-triggered drug release, and cooperative photothermal-chemotherapy function. By grafting the easily self-assembled CuS@polydopamine (CuS@PDA) nanocapsulation with polyacrylic acid (PAA), an inorganic-organic-polymeric hybrid nanovehicle was developed as a dual photothermal agent and carrier for loading antitumor drug-doxorubicin (DOX) through electrostatic adsorption and chemical linking antibody against GPC3 commonly overexpressed in HCC, resulting in the nanodrug, CuS@PDA/PAA/DOX/GPC3. The multifunctional nanovehicle had excellent biocompatibility, stability, and high photothermal conversion efficiency, due to the rationally designed binary CuS@PDA photothermal agent. The 72-h accumulative drug release in pH5.5 tumor microenvironment can reach up to 84%, far higher than 15% measured in pH7.4 condition. Notably, in contrast to the merely 20% survival rate of H9c2 and HL-7702 cells exposed to free DOX, their viabilities in the nanodrug circumstance can maintain 54% and 66%, respectively, suggesting the abated toxicity to the normal cell lines. When exposed to the hepatoma-targeting nanodrug, the viability of HepG2 cells was found to be 36%, which further drastically declined to 10% plus 808-nm NIR irradiation. Moreover, the nanodrug is potent to cause tumor ablation in HCC-modeled mice, and the therapeutic efficacy can be greatly enhanced under NIR stimulus. Histology analyses reveal that the nanodrug can effectively alleviate the chemical damage to heart and liver, as compared to free DOX. This work thus offers a facile strategy for design of targeting anti-HCC nanodrug toward combined photothermal-chemotherapy.

Dual-drug loaded hybrid nanoparticle for combined tumor cocktail chemo-photothermal therapy and anti-inflammation

Dual-drug loaded hybrid nanoparticle for combined tumor cocktail chemo-photothermal therapy and anti-inflammation

Thermosensitive TMPO-oxidized lignocellulose/cationic agarose hydrogel loaded with deferasirox nanoparticles for photothermal therapy in melanoma

Deferasirox (DFX) is an iron-chelating agent effective in treating various kinds of cancers, which inhibits iron metabolism in cancer cells. The recent study aimed to prepare an injectable thermosensitive hydrogel based on lignocellulose and agarose containing deferasirox-loaded polypyrrole nanoparticles for local drug delivery in a combined chemo-photothermal therapy by laser light irradiation. Polypyrrole nanoparticles containing DFX were made by the emulsification method and optimized. Thermosensitive hydrogels were prepared by quaternary ammonium substituted agarose and TMPO-oxidized lignocellulose at different ratios, and the optimal hydrogel was selected based on gelation time, gelation temperature, and injectability. DFX- loaded polypyrrole nanoparticles were then added to the hydrogel, and the drug release, rheology test, injectability, degradation, and swelling percent, as well as cytotoxicity, and photothermal properties, were studied on B16F10, human melanoma cells. The hydrogel with 2 % anionic lignocellulose and 0.5 % cationic agarose showed the shortest gelation time and the highest mechanical strength. It transferred from a liquid state at 4 °C into a semisolid form at 37 °C with a gelation time of 10.3 min. The nanoparticles loaded in hydrogel showed dose-dependent cytotoxicity. The cytotoxic dose of the drug was reduced by laser light irradiation.

Liposomal Iron Oxide Nanoparticles Loaded with Doxorubicin for Combined Chemo-Photothermal Cancer Therapy

Iron oxide nanoparticle (IONP) possesses unique advantages over other nanoparticles in the use of cancer imaging and therapy. Specifically, it has drawn great attention in the emerging research field of photothermal cancer therapy. Herein, we developed doxorubicin (DOX)-loaded liposomal IONP (Lipo-IONP/DOX) and evaluated in vitro and in vivo their applicability for combined chemo-photothermal cancer therapy. The Lipo-IONP was synthesized by the thin-film evaporation method. The prepared Lipo-IONP was observed as about a 240 nm-sized agglomerate of globular-shaped nanoparticles. The TEM and FT-IR data evidenced the successful formation of liposomal IONP. The superparamagnetic property of the Lipo-IONP was confirmed by the SQUID analysis. The DSC data showed a transition temperature of about 47-48 °C for the mixed lipids composing the Lipo IONP, and the DOX release studies revealed the feasibility of induced burst release of DOX by laser irradiation. The Lipo-IONP/DOX possessed a plasma half-life of 42 min, which could ensure sufficient circulation time for magnetic tumor targeting. The in vivo magnetic targeting enabled a significant increase (6.3-fold) in the tumor accumulation of Lipo-IONP/DOX, leading to greater photothermal effects. Finally, the preliminary efficacy study evidenced the applicability as well as the safety of the Lipo-IONP/DOX for use in combined chemo-photothermal cancer therapy. Overall, the study results demonstrated that the Lipo-IONP/DOX might serve as an effective and safe agent for combined chemo-photothermal cancer therapy.