Chemo-photothermal Combination Therapy Research Articles

Nanogold-loaded chitosan nanocomposites for pH/light-responsive drug release and synergistic chemo-photothermal cancer therapy

Stable and biocompatible nano-agents that stimulate the combined cancer therapy are of great necessity. Herein, a ternary system composed of optimally prepared chitosan nanoparticles (ChNPs) efficiently encapsulating 5-Fluorouracil (5-FU) and loaded by gold nanoparticles (AuNPs) was employed for synergistic chemo-photothermal therapy. The composed 5-FU-ChNPs@Au nanocomposites (NCs) combine the features of ChNPs, 5-FU, and AuNPs and exhibit excellent biocompatibility, stability, and killing efficiency of tumor cells. Moreover, its strong absorbance in the visible region promotes the fast release of drug under laser exposure. The synergistic effect of 5-FU-ChNPs@Au was demonstrated in comparison to a variant system (5-FU-ChNPs) which was prepared devoid of AuNPs. The dynamic light scattering of the synthesized NCs verified the high stability and homogeneity of particle size distribution. Cytotoxicity experiments towards hepatocellular carcinoma cells (HepG2) revealed that the combined chemo-photothermal therapy of 5-FU-ChNPs@Au featured highly synergistic manner. These findings offer the 5-FU-ChNPs@Au NCs as a highly potential chemo-photothermal therapeutic platform.

β-Cyclodextrin-cholic acid-hyaluronic acid polymer coated Fe3O4-graphene oxide nanohybrids as local chemo-photothermal synergistic agents for enhanced liver tumor therapy

Synergistic photochemical therapy with high performance and weak side effects is of great importance in hepatocellular carcinoma (HCC) treatment, therefore ingenious construct of nano-based therapy agents with accurate drug delivery and high photothermal conversion efficiency is of critical to the cancer therapy. Herein, an organic-inorganic hybrid nanomaterial (MGO@CD-CA-HA) has been constructed successfully by coating the β-cyclodextrin-cholic acid-hyaluronic acid polymer (CD-CA-HA) onto the Fe3O4-graphene oxide (MGO). The MGO@CD-CA-HA revealed satisfactory multiple-targeted features including the cholic acid supplied hepatic-target, CD44-receptor target of hyaluronic acid and magnetic target of Fe3O4. Meanwhile, the hydrophobic antitumor drug camptothecin (CPT) was easily loaded by MGO@CD-CA-HA to form the MGO@CD-CA-HA/CPT nanocomposite, and the maximum theoretical adsorption capacity can reach 847.4 mg/g. Based on the facile photothermal response of MGO, the near-infrared radiation (808 nm) induced local hyperthermia was directly generated the apoptosis of tumor cells while triggered the release of CPT. Comparing with other kinds of cancer cells and normal hepatocyte cells, this PCT system provides a significant inhibitory effect for the liver cancer cells in vitro. Furthermore, the synergistic photochemical therapy presented the strong antitumor effect (the tumor inhibition rate > 90 %) in vivo. Thus, this study provided a promising multiple-targeted nanocarrier for chemo-photothermal combination therapy of liver cancer.

Construction of a pH- and near-infrared irradiation-responsive nanoplatform for chemo-photothermal therapy.

Au nanoclusters, decorated with graphene quantum dots (GQDs), were obtained through photocatalytic reduction of AuCl43- by UV irradiation, and then cytarabine (Cyt) was loaded to the Au/GQDs via charge-dipole interactions. Mercaptopropionic acid (MPA) was anchored to the Cyt-loaded Au/GQDs through the formation of Au-S bond, which was further encapsulated by polyethyleneimine (PEI) via charge-dipole interactions. The delivery of Cyt from the quaternary complex (Au/GQDs/MPA/PEI) is pH-sensitive and can be modulated by near-infrared (NIR) irradiation. The results of cell viability test indicate that the developed nanoplatform can be used for chemo-photothermal combination therapy of cancer cells, and the efficacy of chemo-photothermal combination therapy is significantly higher than that of the single mode of photothermal therapy (PTT) or chemotherapy.

TPGS/hyaluronic acid dual-functionalized PLGA nanoparticles delivered through dissolving microneedles for markedly improved chemo-photothermal combined therapy of superficial tumor

Nanoparticles (NPs) have shown potential in cancer therapy, while a single administration conferring a satisfactory outcome is still unavailable. To address this issue, the dissolving microneedles (DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy (PTT). α-Tocopheryl polyethylene glycol succinate (TPGS)/hyaluronic acid (HA) dual-functionalized PLGA NPs (HD10 NPs) were fabricated to co-load paclitaxel and indocyanine green. HD10 NPs significantly enhanced the cytotoxicity of low-dose paclitaxel because of active and mitochondrial targeting by HA and TPGS, respectively. PTT could further sensitize tumor cells toward chemotherapy by promoting apoptosis into the advanced period, highly activating caspase 3 enzyme, and significantly reducing the expression of survivin and MMP-9 proteins. Further, the anti-tumor effects of HD10 NPs delivered through different administration routes were conducted on the 4T1 tumor-bearing mice. After a single administration, HD10 NPs delivered with DMNs showed the best anti-tumor effect when giving chemotherapy alone. As expected, the anti-tumor effect was profoundly enhanced after combined therapy, and complete tumor ablation was achieved in the mice treated with DMNs and intra-tumor injection. Moreover, DMNs showed better safety due to moderate hyperthermia. Therefore, the DMNs along with combined chemo-photothermal therapy provide a viable treatment option for superficial tumors.

Construction of bifunctional living red blood cells for combined photothermal-chemotherapy

Modifying living cells using in-situ synthesized nanomaterials to endow them with new functions is highly desirable. Herein we report intra- and extra-cellular dual-modified red blood cells (RBCs) with intracellular CaCO3 nanoparticles (NPs) and extracellular polypyrrole-folic acid (PPy-FA) coating, which are exploited as a bifunctional drug carrier. The functionalized living cells (CaCO3@RBC@PPy-FA) are fabricated through first the intracellular in situ reaction of exogenous Ca2+ and CO32− ions to generate CaCO3 NPs, then polymerization of pyrrole and finally modification of folic acid (FA) on the membrane of individual cells, forming a CaCO3@RBC@PPy-FA structure. As a result, such dual-modified RBCs not only preserve the original performances of the cells but also possess the desirable properties as a drug carrier, such as high loading capacity due to the action of CaCO3 NPs, targeting and light-controlled drug release due to the action of PPy-FA. Under NIR laser stimulation, these bifunctional RBCs (DOX-CaCO3@RBC@PPy-FA) present an instant release profile of doxorubicin (DOX) and have high targeting-ability toward cancer cells, achieving a marked synergistic combined photothermal–chemotherapy effect.

Poly-tannic acid coated paclitaxel nanocrystals for combinational photothermal-chemotherapy

Combinational photothermal-chemotherapy offers great advantages for the treatment of cancer. To achieve this goal, the poly-tannic acid (pTA) coated paclitaxel nanocrystals (PNC) were prepared, which was denoted as PNC-pTA. Herein, paclitaxel (PTX) was prepared as nanocrystals acting as chemo-agent for chemotherapy. And the tannic acid formed a pTA layer coated on PNC in the presence of Fe3+ serving as a potential agent for photothermal therapy (PTT). PNC-pTA was around 470 nm in rod shape and the pTA content was determined to be 11.50 ± 0.48 wt% by mass ratio. pTA exhibited photothermal effect upon laser irradiation of 808 nm, and this effect could be strengthened with the increased amount of Fe3+ in pTA. Moreover, pTA showed excellent photostability under repeated laser irradiation. And with the aid of pTA, the cellular uptake of PNC-pTA was greatly enhanced for different cancerous cell lines. PNC-pTA plus laser irradiation showed much stronger cytotoxicity against the 4T1 cell line compared with that without laser irradiation. And the result of animal experiments showed that PNC-pTA exhibited mild photothermal effect in vivo and the strongest tumor inhibition effect upon laser irradiation compared with single photothermal therapy or chemotherapy. These results confirmed the combinational chemo-photothermal effect of PNC-pTA. Our study provided a versatile platform to achieve combined photothermal-chemotherapy with enhanced therapeutic efficacy.

Construction of all-in-one peptide nanomedicine with photoacoustic imaging guided mild hyperthermia for enhanced cancer chemotherapy

Engineered nanoplatforms for cancer simultaneous imaging and combinational therapy have emerged as a new trend in cancer theranostics. However, molecular engineering of nanomedicines with structure minimization and function maximization are still in acute famine. In this study, a novel kind of supramolecular peptide nanomedicine with all-in-one property was delicately constructed for tumor photoacoustic imaging (PAI) and chemo-photothermal combination therapy. The designed peptide conjugates were easily one-step synthesized with high porphyrin and tyroservatide covalently loading, which self-assembled into supramolecular nanomedicine via non-covalent interactions. Stimulated by the photothermal effect of porphyrin, cancer cells became more susceptive to the chemotherapy drugs of tyroservatide, giving rise to enhanced histone acetylation and cell apoptosis. Moreover, with the assistance of PA imaging guided mild hyperthermia, the in vivo tumor inhibition rate of chemo-photothermal combination therapy with single one injection achieved to 70%, thereby can significantly reduce the doses of chemotherapy. The straightforward preparation process and high biosafety were capable of endowing the designed peptide nanomedicine with great potential for clinical transformation and application. This work provided new insights to fabricate all-in-one supramolecular nanoplatforms based on peptide self-assembly for tumor theranostics.

Self-Assembled Dual-Targeted Epirubicin-Hybrid Polydopamine Nanoparticles for Combined Chemo-Photothermal Therapy of Triple-Negative Breast Cancer.

PurposeFolic acid and cyclic arginylglycylaspartic acid peptides were introduced to the surface of negatively charged lipid-coated hybrid polydopamine-cysteine cores for the delivery of epirubicin (EPI) (E/PCF-NPs). The combined chemo-photothermal therapy using E/PCF-NPs for triple-negative breast cancer was evaluated.Materials and MethodsThe temperature elevation and thermal toxicity of nanoparticles were studied. The morphology and properties of E/PCF-NPs were characterized by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. Physicochemical properties, including particle size, zeta potential, drug loading, entrapment efficiency (EE%), stability and in vitro release, were determined. The cell viability, reactive oxygen species (ROS) levels, ratios of oxidized nicotinamide adenine dinucleotide to its reduced form (NAD+/NADH), apoptosis assays, and cellular uptake of E/PCF-NPs were determined on 4T1 cells. Pharmacokinetic studies and tissue distributions were performed and detected by an ultra-high performance liquid chromatography/mass spectrometry system. The antitumor effects of E/PCF-NPs under near-infrared (NIR) laser irradiation were also evaluated.ResultsThe sphere-like morphology of E/PCF-NPs showed a high EE%, uniform size of 106.7 nm, remarkable stability, and highly improved cytotoxicity under NIR laser, when compared to that of photothermal treatment alone. In vitro release of EPI from E/PCF-NPs was pH sensitive, and a greater response was achieved under NIR laser irradiation. Compared to chemotherapy or photothermal treatment alone, the combined treatment in vitro significantly inhibited the survival rate of 4T1 cells to 17.7%, induced ROS generation, and reduced NAD+/NADH significantly. Treatment with E/PCF-NPs under irradiation induced 4T1 cell apoptosis in approximately 93.6% cells. In vitro cellular uptake of E/PCF-NPs was time-dependent. The long-circulating and higher tumor accumulation of E/PCF-NPs resulted in complete ablation of breast tumor tissue through the enhanced photothermal effect by NIR laser irradiation-mediated cell apoptosis.ConclusionE/PCF-NPs show enhanced anti-cancer effects due to synergistic effects of chemotherapy with photothermal therapy and may be potential therapeutic agents for cancer treatment.

Zinc Ion-Stabilized Aptamer-Targeted Black Phosphorus Nanosheets for Enhanced Photothermal/Chemotherapy Against Prostate Cancer.

Prostate cancer is the second most common malignancy among men worldwide. However, conventional chemotherapy, such as taxane therapy, fails to exhibit efficient treatment for almost half of the patients. In this study, a nano-drug delivery system based on black phosphorus nanosheets (BP NSs) was developed, which was then employed as a multifunctional nanoplatform for targeted combinational chemo-photothermal therapy against prostate cancer. Zinc ion (Zn2+), which has been proven to be able to inhibit prostate cancer cell proliferation, was also introduced into this system. Zn2+ coordination could not only enhance the therapeutic effect of combined chemo-photothermal therapy, but also improve the intrinsic instability of BP NSs through the stabilization of its lone pair electrons. The in vivo study showed the outstanding performance of this system in targeted photothermal/chemotherapy of prostate cancer without side effect to normal organs.

Tumor targeted combination therapy mediated by functional macrophages under fluorescence imaging guidance

Imaging-guiding and targeted drug delivery to tumors are essential for precision cancer therapy, which is a challenging goal to achieve extraordinary therapeutic efficacy. Functional live cells-based delivery systems are expected to play an important role in imaging-guiding and targeted drug delivery. Herein, we fabricated a delivery system mediated by IR-820 conjugated macrophages for tumor targeted combination therapy under fluorescence imaging guidance. The functional macrophages by nature could cross the barriers and recruit into tumors, and serve as host cells to targeted deliver drugs to tumors. The pH-sensitive doxorubicin nanoparticles were engulfed by the macrophages to enhance the drug loading and decrease the damage on host cells. IR-820 was anchored into macrophages cytoplasm to achieve the dual function of photothermal therapy and fluorescence imaging guidance. With Balb/C mice bearing murine breast tumor (4 T1) as models, the functional macrophages for their innate tumor tropism could targeted transport these therapeutic drugs into tumor site to exert efficient chemo-photothermal combination therapy. Moreover, fluorescence imaging-guided drug delivery was employed as the visible strategy to provide the optimized therapeutic window based on the fluorescence of IR-820. The multi-functional macrophages-mediated delivery system would provide a potential for precise and targeted delivery of combination therapy.

Multistimuli-Responsive Polymeric Vesicles for Accelerated Drug Release in Chemo-photothermal Therapy

Multistimuli-responsive nanomedicines present great potential for cancer therapy, as they can be featured as simple, selective, and smart carriers that can release their payload on-demand. In this study, we prepared a multifunctional polymeric vesicular nanocarrier (PVN) based on robust and triple stimuli-responsive micelles that could encapsulate chemotherapeutic drugs (doxorubicin (DOX)) and photothermal agents (IR780 iodide) for combined chemo-photothermal therapy. The size of the PVNs was stable and uniform (∼100 nm), and its DOX and IR780 loading were high: 26.5 and 16.4 wt %, respectively. Further in vitro investigations suggested that the DOX/IR780 coloaded PVNs presented controlled drug release kinetics upon costimulation with specific endogenous stimuli. Upon laser irradiation, DOX/IR780 coloaded PVNs exhibited prominent photothermal cytotoxicity toward murine colon cancer (CT-26) cells. Intracellular uptake assays indicated that DOX/IR780 coloaded PVNs could be readily uptaken by CT-26 cells, resulting in the release of DOX within the cytoplasm of the cells in response to laser irradiation.

In situ formation of metal organic framework onto gold nanorods/mesoporous silica with functional integration for targeted theranostics

In this study, a facile strategy is reported to construct a multifunctional nanocarrier by in situ depositing metal organic framework (MOF) on core-shell gold nanorods-mesoporous silica nanoparticles (GNRs-MSNs). After further modification of hyaluronic acid (HA) on GNRs-MSNs-MOF, the obtained GNRs-MSNs-MA efficiently integrates targeted chemo-photothermal combination therapy and tri-modal magnetic resonance/computed tomography/photoacoustic (MR/CT/PA) imaging into a single platform. The proposed method is also applied to directly grow MOF shell onto core-shell structured MSNs with functional core of magnetic and upconverting nanoparticles. Specifically, GNRs-MSNs-MA exhibits the improved drug loading efficiency and near-infrared (NIR) laser-triggered drug release. The doxorubicin hydrochloride (DOX) loaded GNRs-MSNs-MA (DOX@GNRs-MSNs-MA) is demonstrated with excellent targeted ability toward cancer cells. Accordingly, upon NIR laser irradiation, DOX@GNRs-MSNs-MA also displays outstanding combined efficiency for killing the cancer cell in vitro and suppressing the tumor growth in vivo. The efficient in vivo MR/CT/PA imaging on tumor model is also confirmed. Overall, the fabrication of this multifunctional nanoplatform can provide some insights for integrating MOF with other nanocarriers to realize precise and efficient theranostics.

NIR-Triggered Chemo-Photothermal Therapy by Thermosensitive Gold Nanostar@Mesoporous Silica@Liposome-Composited Drug Delivery Systems

Multimodal therapeutic strategy that combines drug delivery with other treatments (e.g., photodynamic therapy) is highly desired for biomedical applications. Here, we engineer a promising versatile platform based on gold nanostar liposome-entrapped mesoporous silica core-shell nanostructure (GSMS@lip). This system not only served as a container for therapeutic drugs (hydrophilic doxorubicin and hydrophobic docetaxel), but also had high photothermal conversion efficiency. Specifically, the thermosensitive liposome wrapping around mesoporous silica acted as a gatekeeper to encapsulate the drug molecules within the GSMS/Dox/Doc@lip drug delivery system. After exposure to near-infrared (NIR) laser, gold nanostar significantly raised the ambient temperature via photothermal conversion, thereby rupturing the thermosensitive liposomes and subsequently triggering the drug release. Benefiting from the combined chemo-photothermal therapy, this composite system showed enhanced cytotoxicity to MDA-MB-231 and MCF-7 cells. Furthermore, effective drug release and synergistic inhibition of tumor growth were achieved after intratumoral injection of GSMS/Dox/Doc@lip followed by NIR laser irradiation. The proposed multifunctional drug delivery system is capable of codelivering hydrophilic-hydrophobic drugs, providing a potential strategy for multimodal tumor therapies.

Dual-Mode Avocado-like All-Iron Nanoplatform for Enhanced T1/T2 MRI-Guided Cancer Theranostic Therapy.

Development of T1/T2 dual-mode MRI contrast agents that can also treat cancer is an attractive prospect for personalized precision medicine. Unfortunately, conventional contrast agents can suffer from toxicity and lack any ability to treat cancer. An all-iron T1/T2 MR imaging agent with photothermal and drug delivery capability would overcome these issues. Here, an avocado-like Fe3+/Fe2O3 composed T1-T2 dual-mode contrast agent based on Fe-TA coordination network (CNMN) is developed. This material possesses suitable longitudinal and transverse relaxation coefficients. Moreover, the strong heat generation property of Fe-TA endows CNMN with the capability to act as a potent photothermal agent. Furthermore, CNMN can also act as an effective delivery platform for the chemotherapeutic drug doxorubicin (DOX) to achieve high effective chemo-photothermal combination therapy. The work demonstrates reliable T1-T2 MRI-guided chemo-photothermal therapy for safe and effective clinical application.

Chemo-Photothermal Combination Cancer Therapy with ROS Scavenging, Extracellular Matrix Depletion, and Tumor Immune Activation by Telmisartan and Diselenide-Paclitaxel Prodrug Loaded Nanoparticles.

Extracellular matrix (ECM) accumulating in the tumor microenvironment (TME) is generated by tumor-associated fibroblasts. It can elevate interstitial fluid pressure and form dense barriers in tumor tissues. Consequently, nanocarriers are hindered from permeating into deeper tumor sites. Thus, the programmed drug-releasing nanoparticles, G(TM)PPSP, were developed for TME remodeling and breast cancer therapy. Gelatin nanoparticles were linked with platinum nanoparticles (PtNPs) to obtain G(TM)PPSP with a size of 214.0 ± 5.0 nm. Telmisartan (TM) was loaded in gelatin nanoparticles. Paclitaxel (PTX) was attached to PtNPs via a dual redox responsive diselenide bond. TM release was mediated by MMP-2 because of gelatin degradation in TME, and then intracellular PTX was released because of diselenide linkage fracture triggered by ROS or glutathione. ECM was depleted owing to TGF-β downregulation by TM and direct ablation by the photothermal effect of PtNPs. 4T1 tumor progression was inhibited by PTX chemotherapy, intracellular ROS scavenging of PtNPs, and photothermal therapy (PTT). The tumor spheroid penetration assay proved G(TM)PPSP could permeate into deep tumor regions when MMP-2 existed. In vivo antitumor experiments implied G(TM)PPSP with PTT could inhibit tumor growth effectively and remodel TME via ECM depletion and immunity activation, indicating the potential of G(TM)PPSP-based chemo-photothermal combination therapy for breast cancer treatment.

LHRH/TAT dual peptides-conjugated polymeric vesicles for PTT enhanced chemotherapy to overcome hepatocellular carcinoma

Combination therapy such as photothermal therapy (PTT) enhanced chemotherapy is regarded as a promising strategy for cancer treatment. Herein, we developed redox-responsive polymeric vesicles based on the amphiphilic triblock copolymer PCL-ss-PEG-ss-PCL. To avoid the limited therapeutic effect of chemotherapeutic drugs caused by systemic exposures and drug resistance, the redox-sensitive polymeric vesicles were cargoed with two chemotherapeutics: doxorubicin (DOX) and paclitaxel (PTX). Besides, indocyanine green (ICG) was encapsulated, and cell-penetrating peptides and LHRH targeting molecule were modified on the surface of polymeric vesicles. The results indicated that the polymeric vesicles can load different kinds of drugs with high drug loading content, trigger drug release in responsive to the reductive environment, realize high cellular uptake via dual peptides and laser irradiation, and achieve higher cytotoxicity via chemo-photothermal combination therapy. Hence, the redox-responsive LHRH/TAT dual peptides-conjugated PTX/DOX/ICG co-loaded polymeric micelles exhibited great potential in tumor-targeting and chemo-photothermal therapy.

Targeted gold nanoshelled hybrid nanocapsules encapsulating doxorubicin for bimodal imaging and near-infrared triggered synergistic therapy of Her2-positve breast cancer.

A multifunctional targeted nanoplatform combining photothermal therapy and chemotherapy has emerged as a promising strategy for comprehensive therapies of breast cancer. In this study, we constructed human epidermal growth factor receptor 2 (Her2)-targeted gold nanoshelled poly(lactic-co-glycolic acid) hybrid nanocapsules encapsulating perfluorooctyl bromide, superparamagnetic iron oxide nanoparticles, and doxorubicin (Her2-GPDH nanocapsules) as theranostic agent for bimodal ultrasound/magnetic resonance imaging and synergistic photothermal-chemotherapy of Her2-postive breast cancer cells. Her2-GPDH nanocomposites possessed well-defined spherical morphology, and the average diameter was about 296 nm with good dispersion. Targeting assays demonstrated that Her2-GPDH nanocapsules exhibited higher targeting binding to Her2-positive SKBR3 cells than Her2-negative MDA-MB-231cells. The encapsulation efficiency and the loading content of doxorubicin in Her2-GPDH nanocapsules were 39 ± 1.45% and 3.8 ± 0.52%, respectively, and the agent exhibited pH-responsive and near-infrared light-triggered stepwise release behavior of doxorubicin. In vitro, the agent had potential to serve as feasible candidate for ultrasound imaging and T2-weighted magnetic resonance imaging with a relatively high relaxivity. Cell experiments confirmed that the agent had significant photothermal cytotoxicity on SKBR3 cells, and the combined photothermal-chemotherapy could significantly enhance the anti-tumor effect. In summary, the present Her2-GPDH nanocapsules, a novel multifunctional nanoplatform, will offer a new way for early bimodal molecular-level diagnosis and synergistic treatment of Her2-positve breast cancer.

Lactosylated IR820/DOX Co-Assembled Nanodrug for Synergetic Antitumour Therapy.

IntroductionSynergistic treatment integrating photothermal therapy (PTT) and chemotherapy is a promising strategy for hepatocellular carcinoma (HCC). However, the most commonly used photothermal agent, IR820, and chemotherapeutic drug, doxorubicin hydrochloride (DOX), are both hydrophilic molecules that suffer from the drawbacks of a short circulation time, rapid elimination and off-target effects.Methods and ResultsHerein, a novel nanodrug that combined HCC-targeted IR820 and DOX was developed based on excipient-free co-assembly. First, lactosylated IR820 (LA-IR820) was designed to target HCC. Then, the LA-IR820/DOX nanodrug (LA-IR820/DOX ND) was purely self-assembled without excipient assistance. The physicochemical properties and the chemo-photothermal antitumour activity of the excipient-free LA-IR820/DOX ND were evaluated. More importantly, the obtained LA-IR820/DOX ND exhibited 100% drug loading, remarkable HCC targeting and excellent antitumour efficacy.ConclusionThis excipient-free LA-IR820/DOX ND may be a promising candidate for the synchronous delivery and synergistic targeting of IR820 and DOX as a combined chemo-photothermal therapy.

Multifunctional HNT@Fe3O4@PPy@DOX Nanoplatform for Effective Chemo-Photothermal Combination Therapy of Breast Cancer with MR Imaging.

Multifunctional nanoparticles for imaging and treatment in cancer are getting more and more attention recently. Herein, halloysite nanotubes (HNTs), natural clay nanotubes, are designed as multifunctional nanoplatform for targeted delivering photothermal therapy agents and chemotherapeutic drugs. Fe3O4 was anchored on the outer surfaces of HNTs and then doxorubicin (DOX) was loaded on the nanotubes. Afterward, a layer of polypyrrole (PPy), as photothermal agent, was wrapped on the tubes. The nanoplatform of HNT@Fe3O4@PPy@DOX can be guided to tumor tissue by an external magnetic field, and then performs chemo-photothermal combined therapy by 808 nm laser irradiation. HNT@Fe3O4@PPy@DOX shows the ability of T2-weighted magnetic resonance imaging, which could be considered as a promising application in magnetic targeting tumor therapy. In vitro and in vivo experiments demonstrate that HNTs nanoplatform has good biocompatibility and produces a strong antitumor effect trigged by near-infrared laser irradiation. The novel chemo-photothermal therapy nanoplatform based on HNTs may be developed as a multifunctional nanoparticle for imaging and therapy in breast cancer.

Mitoxantrone as photothermal agents for ultrasound/fluorescence imaging-guided chemo-phototherapy enhanced by intratumoral H2O2-Induced CO

Multimodal imaging integrated theranostic nanomaterials provides broad prospects for noninvasive and precise cancer treatment. However, the uncertain physiological metabolism of the existing phototherapy nanoagents greatly prevents its clinical application. Herein, a smart nanoplatform based on clinically chemotherapeutic drugs mitoxantrone (MTO) was prepared to realize ultrasound/fluorescence imaging-guided chemo-photothermal combined therapy. The nanoplatform encapsulating MTO and manganese carbonyl (MnCO), which denoted as MCMA NPs, could accumulate at tumor sites by enhanced permeability and retention (EPR) effect and effectively induce cell apoptosis. MTO with near-infrared absorption (~676 nm) not only acted as chemotherapy drug, but also served as photothermal reagent with high photothermal conversion efficiency (ƞ = 42.2%). Especially, H2O2 in tumor sites and the photothermal effect of MTO could trigger MnCO to generate CO, which made cancer cells more sensitive to MTO and significantly alleviated cell resistance. Simultaneously, CO released in tumor also could act as contrast agent for tumor ultrasound imaging to provide accurate guidance for anticancer treatment. Moreover, MCMA NPs could further promote oxidative stress damage in mitochondria and protect normal cells from side effects of chemotherapy. Both in vivo and in vitro studies indicated that MCMA NPs possessed excellent synergetic tumor inhibition ability with high efficiency and low chemotherapy resistance.