Effects of Fluorinated Functionalization of Linker on Quercetin Encapsulation, Release and Hela Cell Cytotoxicity of Cu-Based MOFs as Smart pH-Stimuli Nanocarriers.

Controlled delivery of target molecules is required in many medical and chemical applications. For such purposes, metal-organic frameworks (MOFs), which possess desirable features such as high porosity, large surface area, and adjustable functionalities, hold great potential as drug carriers. Herein, Quercetin (QU), as an anticancer drug, was loaded on Cu2 (BDC)2 (DABCO) and Cu2 (F4 BDC)2 )DABCO) MOFs (BDC=1,4-benzenedicarboxylate and DABCO=1,4-diazabicyclo[2.2.2]octane). As these Cu-MOFs have a high surface area, an appropriate pore size, and biocompatible ingredients, they can be utilized to deliver QU. The loading efficiency of QU in these MOFs was 49.5 % and 41.3 %, respectively. The drug-loaded compounds displayed sustained drug release over 15 days, remarkably high drug loading capacities and pH-controlled release behavior. The prepared nanostructures were characterized by different characterization technics including FT-IR, PXRD, ZP, TEM, FE-SEM, UV-vis, and BET. In addition, MTT assays were carried out on the HEK-293 and HeLa cell lines to investigate cytotoxicity. Cellular apoptosis analysis was performed to investigate the cell death mechanisms. Grand Canonical Monte Carlo simulations were conducted to analyze the interactions between MOFs and QU. Moreover, the stability of MOFs was also investigated during and after the drug release process. Ultimately, kinetic models of drug release were evaluated.

Fabrication and Evaluation of Ultrasound-Responsive Emulsion Loading Paclitaxel for Targeted Chemotherapy.

Chemotherapy is the most widely used cancer treatment, but it has several drawbacks such as adverse side effects and low bioavailability. To address these limitations, various drug delivery systems have been investigated, including liposomes, micelles, and emulsions. These drug delivery technologies have been improving the efficacy and safety of conventional chemotherapy. This study presents an emerging drug delivery technology for targeted chemotherapy using drug-loaded ultrasound-responsive emulsion (URE) as a drug carrier and ultrasound technology for external activation. URE was designed to be responsive to ultrasound energy and fabricated by using an emulsification technique. To investigate this technology, paclitaxel, as a model drug, was used and encapsulated into URE. The size distribution, morphology, and drug release behavior of paclitaxel-loaded URE (PTX-URE) were characterized, and the echogenicity of PTX-URE was assessed by using ultrasound imaging equipment. The cellular uptake and cytotoxicity of PTX-URE with ultrasound were evaluated in breast cancer cells (MDA-MB-231). Our in vitro results indicate that the combination of PTX-URE and ultrasound significantly enhanced cellular uptake by 10.6-fold and improved cytotoxicity by 24.1% compared to PTX alone. These findings suggest that the URE platform combined with ultrasound is a promising technology to improve the drug delivery efficiency for chemotherapy.

Construction of Core-Cross-Linked Polymer Micelles with High Biocompatibility and Stability for pH/Reduction Controllable Drug Delivery.

Polymer micelles have been studied extensively in drug delivery systems (DDS), and their stability is well known to directly affect drug delivery. In this article, a series of amphiphilic copolymers LA-PDPAn-PVPm were synthesized to prepare core-cross-linked nanoparticles (CNP) applied to controllable and targeted anticancer drug delivery. The copolymers could self-assemble in aqueous solution and form homogeneous spherical micelles with particle sizes of between 100 and 150 nm. A comparison between un-cross-linked UCNP and CNP showed that the cross-linking of LA could significantly improve the stability and responsive ability of the nanoparticles. From the in vitro-simulated drug release experiments, CNP was found to have great drug blocking ability under normal physiological conditions and could achieve rapid and efficient drug release under acidic/reducing conditions. In addition, cell experiments showed that CNP had superior biocompatibility and could target tumor cells for drug release. In conclusion, a drug carrier based on copolymer LA-PDPA-PVP realized effective controlled drug release due to the cross-linking of LA. The results will provide guidance for the design strategy of polymer micelles for drug carriers.

Titanium Carbide MXene Quantum Dots-Modified Hydroxyapatite Hollow Microspheres as pH/Near-Infrared Dual-Response Drug Carriers.

Titanium carbide MXene quantum dots (MQDs) possess intrinsic regulatory properties and selective toxicity to cancer cells. Here, MDQs were selected for the modification of hydroxyapatite (HA) microspheres, and MXene quantum dots-modified hydroxyapatite (MQDs-HA) hollow microspheres with controllable shapes and sizes were prepared as bone drug carriers. The results show that the prepared MQDs-HA hollow microspheres had a large BET surface area (231.2 m2/g), good fluorescence, and low toxicity. In addition, MQDs-HA showed a mild storage-release behavior and good responsiveness of pH and near-infrared (NIR). Thus, the MQDs-HA hollow microspheres have broad application prospects in the field of drug delivery and photothermal therapy.

Self-Luminescent Drug Delivery Vehicle: Synthesis, Self-Assembly Behavior, Cysteine-Responsive Property, and Application in the Visualization of Drug Release.

Targeted drug delivery systems have gained great attention from the chemistry and biomedical fields in recent years due to the minimized harm to normal cells. When designing targeted drug delivery systems, the property of harmlessness to normal cells and the tracking ability of the whole process are quite crucial. These two characters can be brought into the related systems by applying a drug carrier that is self-luminescent and its drug release can be induced by the microenvironment of cancer cells. Therefore, the design and synthesis of drug delivery vehicles are significant for the fabrication of target drug delivery systems. Herein, we have synthesized a cysteine-responsive and fluorescent molecule, maleic acid-modified tetraphenylethylene derivative (MATPE), by a facile method. In addition, a drug delivery system with self-luminescence and cysteine-responsiveness based on the self-assembly of MATPE was fabricated. In this system, MATPE and cysteine both played dual roles as cysteine probe/drug carrier and emission-enhanced inducement/drug-release stimulus. The drug-release process was successfully realized in cancer cells and can be visualized, exhibiting great potential in the field of theranostics.

Injectable Thermosensitive Nanocomposites Based on Poly(N-vinylcaprolactam) and Silica Particles for Localized Release of Hydrophilic and Hydrophobic Drugs.

The systemic delivery of drugs employed by conventional methods has shown to be less effective than a localized delivery system. Many drugs have the effectiveness reduced by fast clearance, increasing the amount required for an efficient treatment. One way to overcome this drawback is through the use of thermoresponsive polymers that undergo a sol-gel transition at physiological temperature, allowing their injection directly in the desired site. In this work, thermosensitive nanocomposites based on poly(N-vinylcaprolactam) and silica particles with 80 and 330 nm were synthesized to be employed as delivery systems for hydrophobic (naringin) and hydrophilic (doxorubicin hydrochloride) drugs. The insertion of SiO2 increased the rheological properties of the nanocomposite at 37 °C, which helps to prevent its diffusion away from the site of injection. The synthesized materials were also able to control the drug release for a period of 7 days under physiological conditions. Due to its higher hydrophobicity and better interaction with the PNVCL matrix, naringin presented a more controlled release. The Korsmeyer-Peppas model indicated different release mechanisms for each drug. At last, a preliminary in vitro study of DOX-loaded nanocomposites cultured with L929 and MB49 cells showed negligible toxic effects on healthy cells and better efficient inhibition of carcinoma cells.

Multiresponsive Keratin-Polysulfobetaine Conjugate-Based Micelles as Drug Carriers with a Prolonged Circulation Time.

A protein-polymer conjugate combines the chemical properties of a synthetic polymer chain with the biological properties of a protein. In this study, the initiator terminated with furan-protected maleimide was first synthesized through three steps. Then, a series of zwitterionic poly[3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate] (PDMAPS) was synthesized via atom transfer radical polymerization (ATRP) and optimized. Subsequently, well-controlled PDMAPS was conjugated with keratin via thiol-maleimide Michael addition. The keratin-PDMAPS conjugate (KP) could self-assemble in an aqueous solution to form micelles with low critical micelle concentration (CMC) values and good blood compatibility. The drug-loaded micelles exhibited triple responsiveness to pH, glutathione (GSH), and trypsin under tumor microenvironments. In addition, these micelles showed high toxicity against A549 cells while low toxicity on normal cells. Furthermore, these micelles performed prolonged blood circulation.

Injectable Hydrogels of Amphiphilic Vitamin E Derivatives for Locoregional Chemotherapy.

Vitamin E derivatives are particularly effective in chemotherapy drug development because they are nontoxic, biocompatible, and selective. Among them, α-tocopheryl succinate (α-TOS) can act synergistically with some chemotherapeutic agents. However, its hydrophobicity limits its systemic administration, and localized formulations are not available. Herein, we developed an injectable hydrogel based on self-assembled micelles of a triblock amphiphilic derivative of α-TOS (PEG-2VES), in which doxorubicin (DOX) was encapsulated in the core of the micelles for combined chemotherapy. A molecule of α-TOS was grafted onto each end of poly(ethylene glycols) (PEGs) of different lengths. Hydrogels were prepared by dissolving the polymers or the DOX-loaded micelles in water at room temperature. The subcutaneously injected hydrogels kept their shape and sustainably released the payloads over 7 days without any noticeable inflammatory response. In vitro and in vivo results confirmed the synergistic antitumor effects of the hydrogel and loaded drug. Furthermore, DOX-loaded hydrogels showed greater therapeutic efficiency and fewer toxic side effects than DOX alone. Overall, this hydrogel acts as a multifunctional system that can deliver drug, improve the therapeutic effect, and minimize drug toxicity.

Zwitterionic Targeting Doxorubicin -Loaded Micelles Assembled by Amphiphilic Dendrimers with Enhanced Antitumor Performance.

Chemotherapy is the main method of treating malignant tumors in clinical treatment. However, the commonly used chemotherapeutic drugs have the disadvantages of high biological toxicity, poor water solubility, low targeting ability, and high side effects. Zwitterionic micelles assembled by amphiphilic dendrimers modified with zwitterionic groups and targeting ligand should largely overcome these shortcomings. Herein, the zwitterionic group and targeting peptide c(RGDfC) were modified on the surface of generation 2 poly(propylene imine) dendrimers (G2 PPI), which was conjugated with hydrophobic N-(2-mercaptoethyl) oleamide to form amphiphilic dendrimers (PPIMYRC). PPIMYRC self-assembled into micelles with doxorubicin (DOX) loaded in the interior of micelles to prepare DOX-loaded micelles (PPIMYRC-DOX micelles). The PPIMYRC-DOX micelles had great stability in fibrinogen and pH-responsive drug release. Furthermore, PPIMYRC-DOX micelles had higher cellular uptake rates than free DOX, resulting in higher cytotoxicity of PPIMYRC-DOX micelles than that of free DOX. More importantly, PPIMYRC-DOX micelles inhibited tumors much better than free DOX. The tumor inhibition rate of PPIMYRC-DOX micelles was as high as 93%. Taken together, PPIMYRC-DOX micelles were assembled by amphiphilic dendrimers with the zwitterionic and targeting groups, which enhanced the therapeutic effect of DOX and reduced its side effects. The prepared targeting nanodrug has great potential for further application in antitumor therapy.

Fabrication of Dual pH/Reduction-Responsive P(CL-co-ACL)-Based Cross-Linked Polymeric Micelles for PTX Delivery.

To enhance the stability of the polymeric micelles and optimize their drug-controlled release ability, three disulfide-linked polyethylene glycol methyl ether methacrylate-disulfide-poly(ε-caprolactone-co-γ-amine-ε-caprolactone) (PPEGMA-SS-P(CL-co-ACL)) polymers were synthesized and characterized by 1H NMR, GPC, and FT-IR successfully, and their dual pH/reduction-responsive cross-linked polymeric micelles were prepared for paclitaxel (PTX) delivery by using 2,3-dimethylmaleic anhydride (DMMA) as the cross-linking agent. The PTX loading capacity (LC) and encapsulation efficiency (EE) values of the cross-linked micelles formed by PPEGMA8-SS-P(CL47-co-ACL15) achieved were 23.96% and 71.58%, slightly higher than those of un-cross-linked micelles. Both particle sizes of blank micelles and in vitro drug release of PTX-loaded micelles confirmed that compared with those un-cross-linked micelles, the cross-linked micelles were more stable at pH 7.4 + 0 mM DTT, with a PTX cumulative release of 13% at 120 h, while the PTX cumulative release of the cross-linked micelles at pH 5.0 + 10 mM DTT were close to that of un-cross-linked micelles after 60 h, indicating the successful reversible cross-linking and smooth drug release of the cross-linked micelles. The cytotoxicity assay showed that PPEGMA8-SS-P(CL47-co-ACL15) and its cross-linked micelles had low cell cytotoxicity, and both PTX-loaded micelles revealed a certain inhibitory effect on HepG2 cells. These results revealed that the dual pH/reduction-responsive cross-linked polymeric micelles prepared from PPEGMA8-SS-P(CL47-co-DCL15) were a promising candidate for PTX delivery.

Controlled Release of Drug-Encapsulated Protein Films with Various Sodium Dodecyl Sulfate Concentrations.

Protein-based drug carriers are ideal drug-delivery platforms because of their biocompatibility, biodegradability, and low toxicity. Many types and shapes of protein-based platforms, including nanoparticles, hydrogels, films, and minipellets, have been prepared to deliver drug molecules. In this study, protein films containing the desired amounts of doxorubicin (DOX) as cancer drugs were developed using a simple mixing method. The release ratio and rate of DOXs were dependent on the surfactant concentration. The drug release ratio was controlled within the range of 20-90% depending on the amount of the surfactant used. The protein film surface was analyzed using a microscope before and after drug release, and the relationship between the degree of film swelling and the drug release ratio was discussed. Moreover, the effects of cationic surfactants on the protein film were investigated. Non-toxic conditions of the protein films were confirmed in normal cells, while the toxicity of the drug-encapsulated protein film was confirmed in cancer cells. Remarkably, it was observed that the drug-encapsulated protein film could eliminate 10-70% of cancer cells, with the extent of efficacy varying based on the surfactant amount.

Exploring Steroidal Surfactants as Potential Drug Carriers for an Anticancer Drug Curcumin: An Insight into the Effect of Surfactants' Structure on the Photophysical Properties, Stability, and Activity of Curcumin.

Despite having tremendous medicinal benefits, the practical applications of curcumin are limited, owing to two major challenges: poor aqueous solubility and lack of bioavailability. In this regard, biosurfactant-based micellar systems have surged recently for the development of novel and more effective formulations because of their biological relevance. This study deals with a comprehensive and comparative investigation on the effect of seven structurally different steroidal surfactants on the photophysical properties of curcumin and also evaluates these steroidal surfactants as possible drug delivery media for curcumin. The photophysical properties of curcumin exhibited a strong dependence on the structure of the steroidal surfactant; the extent of excited-state proton transfer between curcumin and the surfactants depends strongly on the type of the side chain in the surfactants, which mostly dictates the photophysics of curcumin in the presence of these structural variants. The solubility of curcumin and its stability at different pHs and temperatures and in the presence of salt are significantly enhanced in the presence of these surfactants. Furthermore, the curcumin-loaded micelles exhibited improved intracellular uptake and cytotoxicity against MCF-7 cancer cells than pristine curcumin. Among these steroidal surfactants, CHAPS, the zwitterionic derivative of cholic acid, was the most efficient one to offer better solubility and stability to curcumin under all conditions, and the death rate of MCF-7 cells by curcumin was found to be the highest in the presence of CHAPS, indicating the enhanced bioavailability of curcumin. Therefore, CHAPS-based colloids are found to be promising candidates as potential drug carriers for curcumin.

Impact of solid lipid nanoparticles on 3T3 fibroblasts viability and lipid profile: The effect of curcumin and resveratrol loading.

This study focused on the impact in 3T3 fibroblasts of several types of empty and curcumin- and resveratrol-loaded solid lipid nanoparticles (SLN) on cell viability and lipid metabolism in relation to their lipid content and encapsulated drug. SLN, prepared by hot homogenization/ultrasonication, were characterized with respect to size, polydispersity index, and zeta potential. Compritol® 888 ATO at different concentrations (4%, 5%, and 6% wt/wt) was chosen as lipid matrix while Poloxamer 188 (from 2.2% to 3.3% wt/wt) and Transcutol (TRC; 2% or 4%) were added as nanoparticle excipients. Prepared SLN were able to encapsulate high drug amount (encapsulation efficiency percentage of about 97-99%). All empty SLN did not show cytotoxicity (by MTT assay, at 24 h of incubation) in 3T3 cells independently of the lipid and TRC amount, while a viability reduction in the range 5-11% and 12-27% was observed in 3T3 cells treated with curcumin-loaded and resveratrol-loaded SLN, respectively. SLN without TRC did not affect cell lipid metabolism, independently from the lipid content. Empty and loaded SLN formulated with 4% of Compritol and 4% of TRC significantly affected, after 24 h of incubation at the dose of 5 µl/ml, cell polar lipids (phospholipids and free cholesterol) and fatty acid profile, with respect to control cells. Loaded compounds significantly modulated the impact of the corresponding empty formulation on cell lipids. Therefore, the combined impact on lipid metabolism of SLN and loaded drug should be taken in consideration in the evaluation of the toxicity, potential application, and therapeutic effects of new formulations.

The role of critical micellization concentration in efficacy and toxicity of supramolecular polymers.

The inception and development of supramolecular chemistry have provided a vast library of supramolecular structures and materials for improved practice of medicine. In the context of therapeutic delivery, while supramolecular nanostructures offer a wide variety of morphologies as drug carriers for optimized targeting and controlled release, concerns are often raised as to how their morphological stability and structural integrity impact their in vivo performance. After intravenous (i.v.) administration, the intrinsic reversible and dynamic feature of supramolecular assemblies may lead them to dissociate upon plasma dilution to a concentration below their critical micellization concentration (CMC). As such, CMC represents an important characteristic for supramolecular biomaterials design, but its pharmaceutical role remains elusive. Here, we report the design of a series of self-assembling prodrugs (SAPDs) that spontaneously associate in aqueous solution into supramolecular polymers (SPs) with varying CMCs. Two hydrophobic camptothecin (CPT) molecules were conjugated onto oligoethylene-glycol (OEG)-decorated segments with various OEG repeat numbers (2, 4, 6, 8). Our studies show that the lower the CMC, the lower the maximum tolerated dose (MTD) in rodents. When administrated at the same dosage of 10 mg/kg (CPT equivalent), SAPD 1, the one with the lowest CMC, shows the best efficacy in tumor suppression. These observations can be explained by the circulation and dissociation of SAPD SPs and the difference in molecular and supramolecular distribution between excretion and organ uptake. We believe these findings offer important insight into the role of supramolecular stability in determining their therapeutic index and in vivo efficacy.

Studies of anticancer activity in vivo and in vitro behaviors of liposomes encapsulated iridium(III) complex.

Iridium(III) complexes have gained great attention in cancer treatment in recent years. In this paper, we designed and synthesized a new iridium(III) complex [Ir(piq)2(DQTT)](PF6) Ir1 (piq = 1-phenylisoquinoline, DQTT = 12-(1,4-dihydroquinoxalin-6-yl)-4,5,9,14-tetraazabenzo[b]triphenylene). The Ir1-loaded PEGylated liposomes (Lipo-Ir1) were prepared using the ethanol injection method. The anticancer activity of the complex and Lipo-Ir1 against SGC-7901 (human gastric adenocarcinoma), A549 (human lung carcinoma), HeLa (human cervical carcinoma), HepG2 (human hepatocellular carcinoma), BEL-7402 (human hepatocellular carcinoma), and normal NIH3T3 (mouse embryonic fibroblasts) was tested by the MTT method. The complex Ir1 shows moderate or low cytotoxicity against the selected cancer cells, whereas the Lipo-Ir1 exhibits high anticancer activity toward the same cancer cells. The apoptosis induced by Lipo-Ir1 was assayed by flow cytometry and Lipo-Ir1 induced apoptosis through increasing intracellular reactive-oxygen species levels, decreasing mitochondrial membrane potential, further promoting cytochrome c release and causing the increase of level of intracellular Ca2+. Western blot was used to detect the changes in Bcl-2 family protein and PI3K/AKT pathway proteins. The cloning experiments demonstrated that the Lipo-Ir1 can effectively inhibit cell proliferation. In vivo experiments, Lipo-Ir1 inhibited tumor growth in xenograft nude mice, and the percentage of tumor growth inhibition in vivo was 75.70%. Overall, the liposomes Lipo-Ir1 exhibits higher anticancer activity than Ir1 under the same conditions. These results indicated that Lipo-Ir1 may be a valuable resource for cancer therapy.

In silico design and pharmacological evaluation of conjugates of atenolol with modified saccharide for cardiovascular targeting.

Amongst a wide range of biological macromolecules, saccharides exhibit the potential to be specifically recognized by cell-surface receptors and hence can be utilized as ligands in targeted drug delivery. The current study aims to use saccharides viz. Galactose, Pectin and Chitosan to improve targeting of Atenolol by oxalyl chloride mediated grafting. Conjugates were engineered by grafting Atenolol, a cardiovascular agent with the modified saccharide units. The conjugates were characterized by FTIR, DSC and 1H NMR study. Drug release analysis and cellular uptake study was carried out using H9c2 cell lines which represent that concentration of drug in cells treated with all atenolol-saccharide conjugates is enhanced by almost two-folds in comparison with cells treated with atenolol solution. Thus cell line study confers the evidence of selective cardiac delivery. No significant cytotoxicity was observed in case of all synthesized conjugates in the Brine shrimp lethality bioassay. Possible binding of the developed conjugates with the GLUT-4 receptors was assessed by in silico analysis using homology model developed by Swiss Model server. Hence it was concluded that the application of these conjugates with saccharides in selective cardiovascular drug delivery can be a promising approach to increase bioavailability, minimize drug loss by degradation and prevent harmful side effects by increasing specific cell targeting.

Exploring the Toxicity, Lung Distribution, and Cellular Uptake of Rifampicin and Ascorbic Acid-Loaded Alginate Nanoparticles as Therapeutic Treatment of Lung Intracellular Infections.

Nanotechnology is a very promising technological tool to combat health problems associated with the loss of effectiveness of currently used antibiotics. Previously, we developed a formulation consisting of a chitosan and tween 80-decorated alginate nanocarrier that encapsulates rifampicin and the antioxidant ascorbic acid (RIF/ASC), intended for the treatment of respiratory intracellular infections. Here, we investigated the effects of RIF/ASC-loaded NPs on the respiratory mucus and the pulmonary surfactant. In addition, we evaluated their cytotoxicity for lung cells in vitro, and their biodistribution on rat lungs in vivo after their intratracheal administration. Findings herein demonstrated that RIF/ASC-loaded NPs display a favorable lung biocompatibility profile and a uniform distribution throughout lung lobules. RIF/ASC-loaded NPs were mainly uptaken by lung macrophages, their primary target. In summary, findings show that our novel designed RIF/ASC NPs could be a suitable system for antibiotic lung administration with promising perspectives for the treatment of pulmonary intracellular infections.

Use of homoarginine to obtain attenuated cationic membrane lytic peptides.

Our research group has been studying the design of intracellular delivery peptides based on cationic lytic peptides. By placing negatively charged amino acids on potentially hydrophobic faces of the peptides, membrane lytic activity is attenuated on the cell surface, whereas it recovers in endosomes, enabling cytosolic delivery of proteins including antibodies. These lytic peptides generally contain multiple lysines, facilitating cell surface interaction and membrane perturbation. This study evaluated the effect of lysine-to-homoarginine substitution using HAad as a model delivery peptide. The resulting peptide had a comparable or better delivery efficacy for Cre recombinase, antibodies, and the Cas9/sgRNA complex with one-quarter of the concentration of HAad, implying that a subtle structural difference can affect delivery activity.

Facile synthesis of porous MoS2nanofibers for efficient drug delivery and cancer treatment.

Porous MoS2nanofibers were synthesized by electroplating and post-annealing and applied in a responsive drug delivery system. The one-dimensional (1D) MoS2nanofibers displayed a high specific surface area, controllable morphology, and uniform size, serving as a promising drug carrier for chemotherapy. After surface modification with polyethylene glycol (PEG) through PEGylation, the MoS2/PEG composite displayed excellent physical/chemical stability and biocompatibility. More importantly, MoS2/PEG loaded with doxorubicin (DOX) exhibited a controllable release responsive to pH and near-infrared (NIR) irradiation and demonstrated precise DOX dose release. Such remarkable anticancer effects were mainly attributed to outstanding photothermal performance and stability of porous MoS2nanofibers. This work offered a new opportunity of employing porous MoS2nanofibers as drug carriers for effective cancer chemotherapy.

Hollow mesoporous polydopamine nanospheres: synthesis, biocompatibility and drug delivery.

Various polydopamine (PDA) nanospheres were synthesized by utilizing triblock copolymer Pluronic F127 and 1,3,5-trimethylbenzene (TMB) as soft templates. Precise morphology control of polydopamine nanospheres was realized from solid polydopamine nanospheres to hollow polydopamine nanospheres, mesoporous polydopamine nanospheres and hollow mesoporous polydopamine nanospheres (H-MPDANSs) by adjusting the weight ratio of TMB to F127. The inner diameter of the prepared H-MPDANSs can be controlled in the range of 50-100 nm, and the outer diameter is about 180 nm. Furthermore, the thickness of hollow mesoporous spherical shell can be adjusted by changing the amount of dopamine (DA). The H-MPDANSs have good biocompatibility, excellent photothermal properties, high drug loading capacity, and outstanding sustainable drug release properties. In addition, both NIR laser irradiation and acid pH can facilitate the controlled release of doxorubicin (DOX) from H-MPDANSs@DOX.