Chemo-photothermal Therapy Research Articles

MRI-guided dual-responsive anti-tumor nanostructures for synergistic chemo-photothermal therapy and chemodynamic therapy.

Image-guided stimulus-responsive theranostics are beneficial for identifying malignant lesions and integrating multiple cell-killing mechanisms to enhance tumor cell clearance. Herein, an intelligent dual-responsive nanostructure (HSPMH-DOX) was developed for magnetic resonance imaging (MRI)-guided synergistic chemo-photothermal therapy (PTT) and chemodynamic therapy (CDT). The core-shell nanostructure was synthesized by layering polydopamine (PDA), manganese oxide (MnO2), and hyaluronic acid (HA) onto drug-loaded hollow mesoporous silica nanoparticles (HS). The constructed nanoagent has both endogenous and external dual responses. The tumor microenvironment (pH/GSH) can trigger the degradation of gatekeeper (MnO2 and PDA), resulting in the release of anti-tumor drugs, whereas external near-infrared light irradiation can accelerate the degradation process and generate local overheating, resulting in PTT. Notably, MnO2 can not only consume intracellular GSH to enhance CDT but also release Mn2+ for precise localization of tumor tissues using MRI. Both in vitro and in vivo experiments showed that the prepared dual-response nanoagent satisfied biocompatibility, targeting, and the great efficiency of MRI-guided combined therapy. In animal models, combining chemo-PTT and CDT can eradicate tumors in less than two weeks. This work could pave the way for a wide range of stimulus-responsive synergistic theranostic applications, including MRI, chemo-photothermal therapy, and chemodynmic therapy. STATEMENT OF SIGNIFICANCE: Low bioavailability and severe side effects remain the major limitations of conventional cancer chemotherapy. Image-guided combination therapy can alleviate these problems and improve tumor-specific therapy. In the present study, the anticancer drug doxorubicin was encapsulated in a core-shell hollow mesoporous silica nanostructure (HSPMH-DOX), enabling MRI-guided targeted release under both endogenous and external dual stimuli. Moreover, the photothermal and nanoenzymatic effects of nanomedicine can cause local overheating in the tumor and amplify the intracellular CDT effect, accelerating tumor eradication. Systematic evaluations in vitro and in vivo confirmed that nanomedicine enables highly effective MRI-guided synergistic chemo-photothermal and chemodynamic therapy. This work offers a promising therapeutic strategy for precise anti-tumor applications.

Injectable nano-composite hydrogels based on hyaluronic acid-chitosan derivatives for simultaneous photothermal-chemo therapy of cancer with anti-inflammatory capacity

Nowadays, the photothermal therapy (PTT) has received widespread attention and research by rapidly killing tumors with local high temperature. However, due to the irregular edges of tumor and the blurred boundary between normal and necrotic tissues, the desirable treatment cannot be achieved by the single PTT, and excessive heat will cause serious inflammation in local tissues. Herein, an injectable composite hydrogel is prepared by the oxidized hyaluronic acid (OHA) and hydroxypropyl chitosan (HPCS) via the imine bonds, which is employed as the delivery substrate for functional substances. In the gel medium, the mesoporous polydopamine (MPDA) nanoparticles are incorporated as the high efficiency photothermal agent and a reservoir of DOX, which can achieve the good photothermal conversion performance and pulsed drug release. Besides, the addition of the curcumin-cyclodextrin host-guest inclusion complex (CUR@NH2-CD) in the composite hydrogel could reduce the inflammation caused by PTT. The composite hydrogel shows favorable the Hepa1–6 tumor inhibition in vivo by virtue of the comprehensive effect of the admired photothermal efficacy of MPDA, chemotherapy of DOX and anti-inflammatory of CUR. It can be predicted that the composite hydrogel has a broad prospect in the field of comprehensive therapy for tumor.

3D printed hydrogel/bioceramics core/shell scaffold with NIR-II triggered drug release for chemo-photothermal therapy of bone tumors and enhanced bone repair

The treatment of bone defect caused by osteosarcoma remains an intractable problem. Scaffolds with multi-functions are the potential candidates to kill recurrent tumor and to repair the bone defects after tumorectomy. However, most of these scaffolds employed photothermal therapy using near‐infrared laser inthe first biological window (NIR‐I)with intrinsic poor tissue penetration depth. Some scaffolds loading drugs for chemotherapy generally lack the accurate control of on-demand drugs release to reduce the side effects and enhance the therapeutic efficacy. Herein, 3D printed gelatin/bioceramics core/shell scaffolds were developed with doxorubicin (DOX) loaded gelatin as the core part and SrCuSi4O10 (SC) nanosheets/beta-tricalcium phosphate (β-TCP) as the shell part of the printed filaments. SC nanosheets endowed the scaffolds with photothermal therapy under NIR-IIlaser irradiation. Simultaneously, the generated extensive hyperthermia could induce the gel-sol transition of the gelatin in the core part of the filaments, which subsequently triggered the on-demand DOX release from the loosened gelatin achieving chemo-photothermal therapy. The in vitro and in vivo data demonstrated that chemo-photothermal therapy showed a synergetic effect on anti-tumor. Additionally, the degradation/release of gelatin from the filaments resulted in the hollow channels in the scaffold, which provided clear architectural cues for promoting the ingrowth of bone tissues. Meanwhile, the degradation of the SC nanosheets contributed to the sustained release of bioactive ions (Sr, Cu and Si), which further enhanced vascularized bone regeneration. All these results indicated that the 3D printed DOX loaded gelatin-TCP/SC scaffolds had a great potential application for the treatment of bone defects caused by osteosarcoma in effective killing cancer cells and repairing tumor-induced bone defects.

Engineering near-infrared laser-activated gold nanorod vesicles with upper critical solution temperature for photothermal therapy and chemotherapy

Multimodal synergistic therapy based on nanomedicine drug delivery systems can achieve accurate cancer treatment. The anisotropy of gold nanorods (AuNRs) allows the adjustment of the longitudinal localized surface plasmon resonance absorption to the near-infrared band, which shows potential application in the field of photothermal therapy of cancer. Here, we report a new type of thermal-sensitive gold nanorod drug-loaded vesicles (UGRV-DOX) via the self-assembly of AuNRs modified with the amphiphilic polymer (PEG45-b-PS150) and upper critical solution temperature (UCST) polymer (P(AAm-co-AN)). The hollow structure of the vesicle can increase the drug loading capacity, and the polymers on its surface are intertwined to reduce drug leakage. As-prepared UGRV-DOX vesicles exhibits excellent photothermal conversion efficiency and can achieve light-controlled drug release. In vivo anti-tumor experiments showed that UGRV-DOX could ablate HepG2 transplanted tumors significantly under 808 nm laser irradiation, and the inhibition rate was as high as 99.3 %. These tumor-specific nanovesicles prefigure great potentials for high-precision cancer treatment.

Synthesis of Multi-Stimuli Responsive Fe3O4 Coated with Diamonds Nanocomposite for Magnetic Assisted Chemo-Photothermal Therapy

Nanodiamonds with magnetic resonance imaging (MRI) and targeted drug delivery to exert combined effects for biomedical applications have been considered to be an urgent challenge. Herein, a novel bio-nanoarchitectonics (Fe3O4@NDs) with simultaneous imaging and therapeutic capacities was fabricated by covalently conjugating nanodiamonds (NDs) with Fe3O4. Fe3O4@NDs exhibited better biocompatibility and excellent photothermal stability with superb photothermal conversion performance (37.2%). Fe3O4@NDs has high doxorubicin (DOX) loading capacity (193 mg/g) with pH and NIR-responsive release characteristics. Fe3O4@NDs loading DOX showed a combined chemo-photothermal inhibitory effect on the tumor cells. Enhanced T2-weighted MRI contrast toward the tumor, with the assistance of a magnetic field, convinced the Fe3O4@NDs gathered in the tumor more efficiently and could be used for MRI-based cancer diagnosis. Our results revealed an effective strategy to achieve a stimuli-sensitive nanoplatform for multifunctional theranostics by the combined action.

A sequential delivery system based on MoS2 nanoflower doped chitosan/oxidized dextran hydrogels for colon cancer treatment

A sequential delivery system based on MoS2 nanoflower (MoS2 NF) doped chitosan (CS)/oxidized dextran (OD) hydrogels is developed for the treatment of colon cancer. 5-Fluorouracil (5-FU) is combined with polyethylenimine (PEI) decorated MoS2 NF via electrostatic attraction and hydrogen bonding, and the obtained 5-FU/PEI/MoS2 is encapsulated by 1-tetradecanol (TD), a commonly used phase transition material. The resultant TD/5-FU/PEI/MoS2 (TFPM) is then co-encapsulated with methotrexate (MTX) in the CS/OD hydrogels generated via Schiff base reaction and electrostatic attraction. Because the electrostatic attraction between CS and OD is pH-sensitive, MTX and TD/5-FU/PEI/MoS2 can be easily released from the hydrogels at pH 7.4. MoS2 is an outstanding photothermal agent, and the generated hyperthermia under near infrared (NIR) irradiation can lead to the melting of TD and the consequent release of 5-FU encapsulated. More importantly, the generated hyperthermia under NIR irradiation can realize the chemo-photothermal synergistic tumor therapy. Finally, the practicability of the developed sequential delivery system is demonstrated by cytotoxicity test.

Development of Thiol-Maleimide hydrogels incorporating graphene-based nanomaterials for cancer chemo-photothermal therapy

Nano-sized materials have been widely explored in the biomedicine field, especially due to their ability to encapsulate drugs intended to be delivered to cancer cells. However, systemically administered nanomaterials face several barriers that can hinder their tumor-homing capacity. In this way, researchers are now focusing their efforts in developing technologies that can deliver the nanoparticles directly into the tumor tissue. Particularly, hydrogels assembled using Thiol-Maleimide Michael type additions are emerging for this purpose due to their capacity to incorporate high nanoparticles’ doses in a compact 3D structure as well as good chemical selectivity, biocompatibility, and straightforward preparation. Nevertheless, such hydrogels have been mostly prepared using synthetic polymers, which is not ideal due to their poor biodegradability. In this work, a novel natural polymer-based Thiol-Maleimide hydrogel was produced for application in breast cancer chemo-photothermal therapy. To obtain natural polymers compatible with this crosslinking chemistry, Hyaluronic acid was endowed with Thiol groups and deacetylated Chitosan was grafted with Maleimide groups. Parallelly, Doxorubicin loaded Dopamine-reduced graphene oxide (DOX/DOPA-rGO) was prepared for attaining Near Infrared (NIR) light responsive chemo-photothermal nanoagents. By simply mixing Hyaluronic Acid-Thiol, deacetylated Chitosan-Maleimide and DOX/DOPA-rGO, Thiol-Maleimide crosslinked hydrogels incorporating this nanomaterial could be assembled (DOX/DOPA-rGO@TMgel). When breast cancer cells were incubated with DOPA-rGO@TMgel and exposed to NIR light (photothermal therapy), their viability was reduced to about 59 %. On the other hand, DOX/DOPA-rGO@TMgel (chemotherapy) reduced cancer cells’ viability to 50 %. In stark contrast, the combined action of DOX/DOPA-rGO@TMgel and NIR light decreased breast cancer cells’ viability to just 21 %, highlighting its chemo-photothermal potential.

Functionalized Ionic Liquid Exfoliated MoS2 Nanosheets for Photoacoustic Imaging Guided Synergistic Photothermal/Chemotherapy

AbstractNanosheets exhibit highly specific recognition and can be effectively enriched in tumor cells. Controlling nanosheet size and reducing its potential toxicity are key issues in the photothermal therapy of tumors. Herein, a multifunctional nanoplatform based on molybdenum disulfide (MoS2) is developed using a green solvent with antitumor activity, ionic liquid (IL) exfoliation, and surface modification to prepare a few layers of IL‐MoS2 nanosheets, with a lateral dimension of ≈96 nm and thickness of 4 nm. The PEG‐b‐PIL polymer improves the biocompatibility, physiological stability, and biodegradability of the nanosheet, and IL‐MoS2‐PEG‐b‐PIL exhibits good photothermal stability and photothermal effects. The in vitro and in vivo results show that IL‐MoS2‐PEG‐b‐PIL nanosheets synergistically inhibit tumor cell growth in combination with photothermal therapy and chemotherapy under 808 nm laser irradiation. The steady increase in the weight of mice during the treatment indicates that the nanosheets are safe. Therefore, the results confirm that IL‐MoS2‐PEG‐b‐PIL nanosheets exhibit good antitumor effects and provide a promising strategy for clinical cancer treatments.

An Overview on Gold Nanorods as Versatile Nanoparticles in Cancer Therapy.

Gold nanorods (GNRs/AuNRs) are a group of gold nanoparticles which their simple surface chemistry allows for various surface modifications, providing the possibility of using them in the fabrication of biocompatible and functional nano-agents for cancer therapy. AuNRs, moreover, exhibit a maximum absorption of longitudinal localized surface plasmon resonance (LSPR) in the near-infrared (NIR) region which overlaps with NIR bio-tissue 'window' suggesting that they are proper tools for thermal ablation of cancer cells. AuNRs can be used for induction of mono or combination therapies by administering various therapeutic approaches such as photothermal therapy (PTT), photodynamic therapy (PDT), chemotherapy (CT), radiotherapy (RT), and gene therapy (GT). In this review, anticancer therapeutic capacities of AuNRs along with different surface modifications are summarized comprehensively. The roles of AuNRs in fabrication of various nano-constructs are also discussed.

Celastrol Loaded PEGylated Nanographene Oxide for Highly Efficient Synergistic Chemo/Photothermal Therapy.

The main aim of this study is to improve the solubility, reduce side effects and increase the therapeutic efficacy of CSL by using functionalized graphene oxide as a carrier, to fulfill chemo-photothermal therapy. Celastrol (CSL), which is extracted from the traditional Chinese medicinal plant Tripterygium wilfordii, has reported significant antitumor activity in vitro and in vivo cancer models. However, disadvantages with regard to solubility, short plasma half-life and toxicity hinder its use in pharmaceutical application. Nanocarrier delivery system could be employed to improve the biochemical and pharmacokinetic performance of CSL. Among numerous nanocarriers, graphene oxide is one of the most promising nanocarriers due to its intrinsic physical and chemical properties and good biocompatibility. Here, we employed a PEGylated reduced nanographene oxide CSL complex (nrGO-PEG/CSL) as a new drug delivery system to achieve highly efficient synergistic chemo/photothermal therapy. A functionalized nrGO-PEG was synthesized and the loading capacity of CSL, photothermal effect and release efficiency under different pH and NIR irradiation were measured in the first stage of work. In vitro and in vivo anticancer effects of prepared nrGO-PEG/CSL complex were evaluated on 4T1 cells and 4T1 tumor-bearing mice, respectively, with the association of NIR laser irradiation. The functionalized nrGO-PEG exhibited excellent drug loading capacity of CSL (20.76 mg/mg GO) and photothermal effect (~3.0 -fold increment over unreduced nGO-PEG). Loaded CSL could be efficiently released from nrGO-PEG/CSL complex by NIR irradiation in vitro. In vivo study performed on 4T1 tumor-bearing mice proved that nrGO-PEG/CSL with NIR laser irradiation shows superior anticancer effects. The experimental data demonstrated that the nrGO-PEG/CSL-mediated chemo/photothermal combination therapy was more cytotoxic to cancer cells than only chemotherapy or photothermal treatment, reducing the occurrence of tumor metastasis. Therefore, nrGO-PEG/CSL-mediated chemo/photothermal is expected to be a promising treatment for synergistic cancer therapy.

A Multifunctional, Highly Biocompatible, and Double-Triggering Caramelized Nanotheranostic System Loaded with Fe3O4 and DOX for Combined Chemo-Photothermal Therapy and Real-Time Magnetic Resonance Imaging Monitoring of Triple Negative Breast Cancer.

Owing to lack of specific molecular targets, the current clinical therapeutic strategy for triple negative breast cancer (TNBC) is still limited. In recent years, some nanosystems for malignancy treatment have received considerable attention. In this study, we prepared caramelized nanospheres (CNSs) loaded with doxorubicin (DOX) and Fe3O4 to achieve the synergistic effect of combined therapy and real-time magnetic resonance imaging (MRI) monitoring, so as to improve the diagnosis and therapeutic effect of TNBC. CNSs with biocompatibility and unique optical properties were prepared by hydrothermal method, DOX and Fe3O4 were loaded on it to obtain Fe3O4/DOX@CNSs nanosystem. Characteristics including morphology, hydrodynamic size, zeta potentials and magnetic properties of Fe3O4/DOX@CNSs were evaluated. The DOX release was evaluated by different pH/near-infrared (NIR) light energy. Biosafety, pharmacokinetics, MRI and therapeutic treatment of Fe3O4@CNSs, DOX and Fe3O4/DOX@CNSs were examined in vitro or in vivo. Fe3O4/DOX@CNSs has an average particle size of 160 nm and a zeta potential of 27.5mV, it demonstrated that Fe3O4/DOX@CNSs is a stable and homogeneous dispersed system. The hemolysis experiment of Fe3O4/DOX@CNSs proved that it can be used in vivo. Fe3O4/DOX@CNSs displayed high photothermal conversion efficiency, extensive pH/heat-induced DOX release. 70.3% DOX release is observed under the 808 nm laser in the pH = 5 PBS solution, obviously higher than pH = 5 (50.9%) and pH = 7.4 (less than 10%). Pharmacokinetic experiments indicated the t1/2β, and AUC0-t of Fe3O4/DOX@CNSs were 1.96 and 1.31 -fold higher than those of DOX solution, respectively. Additionally, Fe3O4/DOX@CNSs with NIR had the greatest tumor suppression in vitro and in vivo. Moreover, this nanosystem demonstrated distinct contrast enhancement on T2 MRI to achieve real-time imaging monitoring during treatment. Fe3O4/DOX@CNSs is a highly biocompatible, double-triggering and improved DOX bioavailability nanosystem that combines chemo-PTT and real-time MRI monitoring to achieve integration of diagnosis and treatment of TNBC.

Fabricating Aptamer-functionalized Ti3C2 therapeutic nanoplatform for targeted chemo-photothermal therapy of cancer

Aptamer (Apt) is a kind of recognition molecule with excellent affinity and high specificity. Transmembrane glycoprotein mucin (MUC1) is an important tumor biomarker overexpressed in MCF-7 tumor cells. MUC1 Apt (Apt-M) could specifically target MCF-7 tumor cells. Ti3C2 nanosheets with high photothermal conversion efficiency were considered as a promising therapeutic nanoplatform for tumor therapy. Doxorubicin (DOX) is a common anti-tumor drug. Herein, a novel DOX/Ti3C2/Apt-M therapeutic nanoplatform was successfully fabricated, which could specifically target MCF-7 tumor cells. As expected, the temperature of DOX/Ti3C2/Apt-M therapeutic nanoplatform raised rapidly under laser irradiation. Meanwhile, chemotherapy was triggered through multimodal stimuli-responsive drug release from the DOX/Ti3C2/Apt-M therapeutic nanoplatform under acidic environment and laser-induced local high temperature. Encouragingly, the MCF-7 cell viability of DOX/Ti3C2/Apt-M with laser irradiation was only 26.9%. The tumor surface temperature of MCF-7 xenograft mice in the DOX/Ti3C2/Apt-M + Laser group rose to about 58.3 °C, which was significantly higher than other laser irradiation groups. The experiments in vitro and in vivo indicated that the DOX/Ti3C2/Apt-M therapeutic nanoplatform can rapidly accumulate in MCF-7 tumors with excellent active targeting properties, and display superior tumor suppressive ability through combination therapy. This work provides a new idea of targeted tumor therapy based on Ti3C2 nanosheets.

Polydopamine-guarded metal-organic frameworks as co-delivery systems for starvation-assisted chemo-photothermal therapy

Cutting off glucose provision by glucose oxidase (GOx) to famish tumors can be an assistance with chemotherapy to eliminate cancer cells. Co-encapsulation of GOx and chemotherapeutics (doxorubicin) within pH-sensitive metal-organic frameworks (MOFs) could disorder metabolic pathways of cancer cells and generate excessive intracellular reactive oxygen species (ROS), together. To prevent premature leach of GOx from the porous channels of MOFs, polydopamine (PDA) was deposited on the surface of MOFs, which endowed the delivery system with photothermal conversion ability. Our nanoscaled co-delivery system (denoted as DGZPNs) remains stable with low amount of drug leakage under simulated physiological conditions in vitro and internal environment, while they are triggered to release doxorubicin (DOX) and GOx in acid tumor microenvironment and at high temperature for reinforced chemotherapy. NIR laser irradiation also activates superior photothermal conversion efficiency of PDA (36.9 %) to initiate hyperthermia to ablate tumor tissue. After being phagocytized by 4 T1 cells (breast cancer cells), the DGZPNs delivery system showed a superior therapeutic efficacy with a tumor growth inhibition of 88.9 ± 6.6 % under NIR irradiation, which indicated that the starvation-assisted chemo-photothermal therapy prompts the significant advance of synergistic therapy in a parallelly controlled mode.

Metal-polyphenol polymer modified polydopamine for chemo-photothermal therapy.

Chemotherapy combined with photothermal therapy (PTT) is a new way to improve the curative effect of cancer treatment. Here, we developed a multifunctional nanoparticle, namely PTX@mPDA@Fe-GA with the loading of a chemotherapeutic drug paclitaxel (PTX) for targeted and synergistic chemotherapy/photothermal therapy in lung cancer. Fe-gallic acid (Fe-GA) was coated on the surface of mesoporous polydopamine (mPDA) nanoparticles, and then the PTX was placed in the mesopores. The drug release of the loaded PTX exhibited pH- and thermal-dual responsive manner. Both mPDA and Fe-GA have high photothermal conversion ability and play a role in photothermal therapy. In addition, the results revealed that mPDA@Fe-GA had excellent biocompatibility and low hemolysis rate. The PTX-loaded mPDA@Fe-GA not only has excellent killing effect on lung cancer cells (A549) in vitro, but also can significantly suppress the growth of A549 subcutaneous tumor in nude mice. In a nutshell, the developed multifunctional nanoparticles integrate photothermal therapy and efficient chemotherapeutic drug delivery, providing new therapeutic ideas in the fight against lung cancer.

Site-specific nanomodulator capable of modulation apoptosis for enhanced colorectal cancer chemo-photothermal therapy

BackgroundColorectal cancer (CRC) is a common malignancy with the second highest mortality and the third highest morbidity worldwide. However, the overall survival of patients is unsatisfactory, thus requiring more effective clinical strategies. Celastrol (CLT), a natural bioactive compound, has been reported to induce reactive oxygen species (ROS)-mediated apoptosis to exhibit significant antitumor effects against CRC. However, the poor water solubility, low targeting ability, and bioavailability of CLT have limited its application, and CLT-induced protective autophagy weakens its therapeutic efficiency.ResultsWe designed a targeted chemo-phototherapy nanoplatform (HCR NPs) to improve the application of CLT. The codelivery of IR820 and CLT in HCR NPs solved the water-soluble problem of CLT and enhanced apoptosis via IR820-mediated hyperthermia. In addition, hydroxychloroquine (HCQ) conjugated to hyaluronic acid (HA) not only increased the active targeting of HCR NPs but also inhibited CLT-induced protective autophagy to exacerbate apoptosis, thus achieving an amplified antitumor effect. Importantly, the HCR NPs exhibited an excellent therapeutic effect on CRC both in vitro and in vivo.ConclusionThe HCR NPs presented in this study may not merely provide a new reference for the clinical application of CLT but also result in an attractive strategy for CRC treatment.

Tetrahedral DNA Nanostructure-modified Gold Nanorod-based Anticancer Nanomaterials for Combined Photothermal Therapy and Chemotherapy

ObjectiveTo develop an effective treatment strategy to simultaneously avoid fatal adverse effects in the treatment of oral cancer, combination therapy has been explored because of its multiple functions. This work aims to develop a novel type of gold-nanorod-based nanomaterials decorated with tetrahedral DNA nanostructures (TDN) carrying antitumor drugs, namely, GNR@TDN-DOX nanocomposites. MethodsIn the designed structure, TDN, with a three-dimensional geometry composed of DNA strands, can provide GC base pairs for binding with the anticancer drug doxorubicin (DOX). The photothermal heating properties, biocompatibility properties, and antitumor performance of obtained GNR@TDN-DOX nanocomposites were investigated to assess their application potential in tumor treatment. ResultsSystematic studies have shown that the obtained GNR@TDN-DOX nanocomposites have high photothermal conversion under the illumination of an 808-nm infrared laser, leading to effective antitumor applications. In addition, the cell viability study shows that GNR@TDN-DOX nanocomposites have good biocompatibility. In vitro studies based on A375 cells show that the GNR@TDN-DOX nanocomposites can effectively eliminate cancer cells because of the combination of photothermal therapy induced by GNRS and chemotherapy induced by TDN-carrying DOX. The result shows that the obtained GNR@TDN-DOX nanocomposites have efficient cellular uptake and lysosome escape ability, together with their nuclear uptake behavior, which results in a significant antitumor effect. ConclusionThis work has demonstrated a potential nanoplatform for anticancer applications.

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.

Hyaluronic Acid-Modified Cisplatin-Encapsulated Poly(Lactic-co-Glycolic Acid) Magnetic Nanoparticles for Dual-Targeted NIR-Responsive Chemo-Photothermal Combination Cancer Therapy.

Combination chemo-photothermal therapy with nanomaterials can reduce the dose of chemotherapeutic drugs required for effective cancer treatment by minimizing toxic side effects while improving survival times. Toward this end, we prepare hyaluronic acid (HA)-modified poly(lactic-co-glycolic acid) (PLGA) magnetic nanoparticles (MNP) for the CD44 receptor-mediated and magnetic field-guided dual-targeted delivery of cisplatin (CDDP). By co-encapsulating the CDDP and oleic acid-coated iron oxide MNP (IOMNP) in PLGA, the PMNPc was first prepared in a single emulsification/solvent evaporation step and successively surface modified with chitosan and HA to prepare the HA/PMNPc. Spherical HA/PMNPc nanoparticles of ~300 nm diameter can be prepared with 18 and 10% (w/w) loading content of CDDP and IOMNP and a pH-sensitive drug release to facilitate the endosomal release of the CDDP after intracellular uptake. This leads to the higher cytotoxicity of the HA/PMNPc toward the U87 glioblastoma cells than free CDDP with reduced IC50, a higher cell apoptosis rate, and the enhanced expression of cell apoptosis marker proteins. Furthermore, the nanoparticles show the hyperthermia effect toward U87 after short-term near-infrared (NIR) light exposure, which can further elevate the cell apoptosis/necrosis rate and upregulate the HSP70 protein expression due to the photothermal effects. The combined cancer therapeutic efficacy was studied in vivo using subcutaneously implanted U87 cells in nude mice. By using dual-targeted chemo-photothermal combination cancer therapy, the intravenously injected HA/PMNPc under magnetic field guidance and followed by NIR laser irradiation was demonstrated to be the most effective treatment modality by inhibiting the tumor growth and prolonging the survival time of the tumor-bearing nude mice.

EGFR-targeted hybrid lipid nanoparticles for chemo-photothermal therapy against colorectal cancer cells

Antibody-functionalized targeted nanocarriers have shown great–potential for minimizing the chemoresistance and systemic toxicity of cancer chemotherapies. The combination of chemotherapy and photothermal therapy has great potential in improving therapeutic effect. However, cetuximab-modified nanoparticles based lipids for chemo-phototherapy of EGFR overexpressing colorectal carcinoma (CRC) have seldom been investigated. Hence, this study aimed to fabricate cetuximab-conjugated and near infrared (NIR) light-responsive hybrid lipid-polymer nanoparticles (abbreviated as Cet-CINPs) for targeted delivery of irinotecan. Cet-CINPs were prepared with copolymer PLGA and various lipids DSPE-PEG, DSPE-PEG-Mal, lecithin as carriers. Cetuximab was conjugated on the surface of nanoparticles to achieve targeting anti-tumor efficacy. Cet-CINPs were characterized in terms of morphology (spherical), size (119 nm), charge (−27.2 mV), drug entrapment efficiency (43.27 %), and antibody conjugation efficiency (70.87 %). Cet-CINPs showed preferable photothermal response, pH/NIR-triggered drug release behavior, enhanced cellular uptake and ROS level compared with free ICG and CINPs. Meanwhile, in vitro cytotoxicity assay showed that Cet-CINPs with NIR irradiation had a higher cytotoxicity against Lovo cells than non-targeted or non-NIR activated nanoparticles. The IC50 values of Cet-CINPs with NIR irradiation was 22.84 ± 1.11 μM for 24 h and 5.01 ± 1.06 μM for 48 h, respectively. These investigations demonstrate that Cet-CINPs with good tumor-targeting ability and enhanced antitumor activity, are a promising multifunctional nanoplatform for CRC therapy.

Enzyme/GSH/pH-responsive hyaluronic acid grafted porous silica nanocarriers bearing Ag2S QDs for fluorescence imaging and combined therapy

Hyaluronic acid (HA) is a naturally polysaccharide that has been used for drug delivery, but is limited by low drug loading capacity and drug leakage in circulation. To improve drug delivery efficient, HA modified porous silica (pSiO2) nanocarriers were successfully prepared for drug delivery and combining therapy. pSiO2 nanocarriers have stable porous structure and high loading capacity, and pSiO2/HA nanocarriers would possess advantages of HA-based carriers and pSiO2 nanoparticles. Herein, pSiO2 nanocarriers were prepared by two-phase process, followed by embedding Ag2S QDs in the pore walls of pSiO2 carriers, which render the carriers photothermal effect. pSiO2 nanocarriers have size of 30 nm, large channels, and high loading capacity (29.3 %). To graft HA, a sensitive linker with alkyl amine and disulfide bond was conjugated on the surface of Ag2S/pSiO2 nanocarriers by three-step reaction. After loading doxorubicin (DOX), HA was grafted via sensitive linker onto the surface of Ag2S/pSiO2 carriers via the formation of amide bonds to seal the loaded drugs. The interaction between HA and CD44 confers the carrier targeting ability to cancer cells. HA coating can be degraded by hyaluronidase resulting in the release of internal cargo. The Ag2S/pSiO2/HA nanocarriers performs responsive drug release and combining photothermal chemotherapy.