High Drug Loading Ability Research Articles

Progress of Drug Nanocrystal Self-Stabilized Pickering Emulsions: Construction, Characteristics In Vitro, and Fate In Vivo.

A drug nanocrystal self-stabilized Pickering emulsion (DNSPE) is a novel Pickering emulsion with drug nanocrystals as the stabilizer. As a promising drug delivery system, DNSPEs have attracted increasing attention in recent years due to their high drug loading capacity and ability to reduce potential safety hazards posed by surfactants or specific solid particles. This paper comprehensively reviews the progress of research on DNSPEs, with an emphasis on the main factors influencing their construction, characteristics and measurement methods in vitro, and fate in vivo, and puts forward issues that need to be studied further. The review contributes to the advancement of DNSPE research and the promotion of their application in the field of drug delivery.

Aptamer-based nanotrains and nanoflowers as quinine delivery systems

In this study, we designed aptamer-based self-assemblies for the delivery of quinine. Two different architectures were designed by hybridizing quinine binding aptamers and aptamers targeting Plasmodium falciparum lactate dehydrogenase (PfLDH): nanotrains and nanoflowers. Nanotrains consisted in controlled assembly of quinine binding aptamers through base-pairing linkers. Nanoflowers were larger assemblies obtained by Rolling Cycle Amplification of a quinine binding aptamer template. Self-assembly was confirmed by PAGE, AFM and cryoSEM. The nanotrains preserved their affinity for quinine and exhibited a higher drug selectivity than nanoflowers. Both demonstrated serum stability, hemocompatibility, low cytotoxicity or caspase activity but nanotrains were better tolerated than nanoflowers in the presence of quinine. Flanked with locomotive aptamers, the nanotrains maintained their targeting ability to the protein PfLDH as analyzed by EMSA and SPR experiments. To summarize, nanoflowers were large assemblies with high drug loading ability, but their gelating and aggregating properties prevent from precise characterization and impaired the cell viability in the presence of quinine. On the other hand, nanotrains were assembled in a selective way. They retain their affinity and specificity for the drug quinine, and their safety profile as well as their targeting ability hold promise for their use as drug delivery systems.

Advances of Cobalt Nanomaterials as Anti-Infection Agents, Drug Carriers, and Immunomodulators for Potential Infectious Disease Treatment.

Infectious diseases remain the most serious public health issue, which requires the development of more effective strategies for infectious control. As a kind of ultra-trace element, cobalt is essential to the metabolism of different organisms. In recent decades, nanotechnology has attracted increasing attention worldwide due to its wide application in different areas, including medicine. Based on the important biological roles of cobalt, cobalt nanomaterials have recently been widely developed for their attractive biomedical applications. With advantages such as low costs in preparation, hypotoxicity, photothermal conversion abilities, and high drug loading ability, cobalt nanomaterials have been proven to show promising potential in anticancer and anti-infection treatment. In this review, we summarize the characters of cobalt nanomaterials, followed by the advances in their biological functions and mechanisms. More importantly, we emphatically discuss the potential of cobalt nanomaterials as anti-infectious agents, drug carriers, and immunomodulators for anti-infection treatments, which might be helpful to facilitate progress in future research of anti-infection therapy.

Advances and Potentials of Polydopamine Nanosystem in Photothermal-Based Antibacterial Infection Therapies.

Bacterial infection remains one of the most dangerous threats to human health due to the increasing cases of bacterial resistance, which is caused by the extensive use of current antibiotics. Photothermal therapy (PTT) is similar to photodynamic therapy (PDT), but PTT can generate heat energy under the excitation of light of specific wavelength, resulting in overheating and damage to target cells or sites. Polydopamine (PDA) has been proved to show plenty of advantages, such as simple preparation, good photothermal conversion effects, high biocompatibility, and easy functionalization and adhesion. Taking these advantages, dopamine is widely used to synthesize the PDA nanosystem with excellent photothermal effects, good biocompatibility, and high drug loading ability, which therefore play more and more important roles for anticancer and antibacterial treatment. PDA nanosystem-mediated PTT has been reported to induce significant tumor inhibition, as well as bacterial killings due to PTT-induced hyperthermia. Moreover, combined with other cancer or bacterial inhibition strategies, PDA nanosystem-mediated PTT can achieve more effective tumor and bacterial inhibitions. In this review, we summarized the progress of preparation methods for the PDA nanosystem, followed by advances of their biological functions and mechanisms for PTT uses, especially in the field of antibacterial treatments. We also provided advances on how to combine PDA nanosystem-mediated PTT with other antibacterial methods for synergistic bacterial killings. Moreover, we further provide some prospects of PDA nanosystem-mediated PTT against intracellular bacteria, which might be helpful to facilitate their future research progress for antibacterial therapy.

A self-assembling prodrug nanosystem to enhance metabolic stability and anticancer activity of gemcitabine

Self-assembly is a powerful approach in molecular engineering for biomedical applications, in particular for creating self-assembling prodrugs. Here, we report a self-assembling prodrug of the anticancer drug gemcitabine (Gem) based on amphiphilic dendrimer approach. The prodrug reported in this study demonstrates high drug loading (40%) and robust ability to self-assemble into small nanomicelles, which increase the metabolic stability of Gem and enable entry into cells via endocytosis, hence bypassing transport-mediated uptake. In addition, this prodrug nanosystem exhibited an effective pH- and enzyme-responsive release of Gem, resulting in enhanced anticancer activity and reduced toxicity. Harboring advantageous features of both prodrug- and nanotechnology-based drug delivery, this self-assembling Gem prodrug nanosystem constitutes a promising anticancer candidate. This study also offers new perspectives of the amphiphilic dendrimer nanoplatforms for the development of self-assembling prodrugs.

Self-assembling combretastatin A4 incorporated protamine/nanodiamond hybrids for combined anti-angiogenesis and mild photothermal therapy in liver cancer

Tumor angiogenesis has been identified as an important factor in the development and progression of tumors, and anti-angiogenesis therapy has been recognized as an effective tumor therapy pattern. The unique characteristics of nanodiamonds (NDs) have been explored for photothermal therapy (PTT) against cancer, while the efficiency of mild PTT mediated by bare NDs was limited. The combination of different therapies into a single nanoplatform has shown great potential for synergistic cancer treatment. In this investigation, we integrated hydrophobic antiangiogenesis agent combretastatin A4 (CA4) into the protamine sulfate (PS) functionalized NDs hybrids (NDs@PS) with a noncovalent self-assembling method (CA4-NDs@PS) for potential combined anti-angiogenesis and mild PTT in liver cancer. The resulted CA4-NDs@PS NDs exhibited high drug loading ability, good dispersibility and colloidal stability. The near-infrared (NIR) laser irradiation could trigger the release of CA4 from CA4-NDs@PS NDs and elevate the temperature of CA4-NDs@PS NDs aqueous solution. In vitro results illustrated that CA4-NDs@PS coupled with laser irradiation could remarkably enhance HepG-2 cells killing efficiency, leading to an enhanced photocytotoxicity. Furthermore, in vivo experiments revealed that CA4-NDs@PS exhibited a highly synergistic anticancer efficacy with NIR laser irradiation in HepG-2 tumor-bearing mice. Altogether, our present study fabricated a novel NDs@PS-based nanoplatform for combined anti-tumor angiogenesis and mild PTT against liver cancer.

Hollow organic/inorganic hybrid nanoparticles from dextran-block-polypeptide copolymer: Double click reaction synthesis and properties

To increase the drug loading and prolong the drug release time, novel hollow organic/inorganic hybrid nanoparticles based on dextran-b-poly(L-glutamate-graft-3-mercaptopropyltrimethoxysilane) (Dex-b-P(ALG-g-MTPMS)) were prepared. First, a polysaccharide block polypeptide diblock copolymer, dextran-block-poly(γ-allyl-L-glutamate) (Dex-b-PALG) bearing allyl side-groups, has been synthesized by the combination of ring-opening polymerization and alkyne-azide [2 + 3] Huisgen's cycloaddition. Next, the allyl side-groups residing in the poly(γ-allyl-L-glutamate) block were further functionalized with 3-mercaptopropyltrimethoxysilane(MPTMS) by radical “thiol-ene” addition reactions. Finally, after a sol-gel process of the obtained copolymers, the novel organic/inorganic hybrid nanoparticles were prepared. The molecular structures, physicochemical, and self-assembly of these copolymers were characterized through FTIR, 1H NMR, dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The cross-linked hybrid nanoparticles have a higher drug loading ability and slower release rate as compared to the uncross-linked counterparts. The MTT evaluation demonstrated that the organic/inorganic hybrid nanoparticles with good biocompatibility.

Schiff-Linked PEGylated Doxorubicin Prodrug Forming pH-Responsive Nanoparticles With High Drug Loading and Effective Anticancer Therapy.

Developing efficacious drug delivery systems for targeted cancer chemotherapy remains a major challenge. Here we demonstrated a kind of pH-responsive PEGylated doxorubicin (DOX) prodrug via the effective esterification and Schiff base reactions, which could self-assemble into the biodegradable micelles in aqueous solutions. Owing to low pH values inside the tumor cells, these PEG-Schiff-DOX nanoparticles exhibited high drug loading ability and pH-responsive drug release behavior within the tumor cells or tissues upon changes in physical and chemical environments, but they displayed good stability at physiological conditions for a long period. CCK-8 assay showed that these PEGylated DOX prodrugs had a similar cytotoxicity to the MCF-7 tumor cells as the free DOX drug. Moreover, this kind of nanoparticle could also encapsulate small DOX drugs with high drug loading, sufficient drug release and enhanced therapeutic effects toward MCF-7 cells, which will be benefited for developing more drug carriers with desirable functions for clinical anticancer therapy.

A Review of Water-Resistant Cellulose-Based Materials in Pharmaceutical and Biomedical Application.

Cellulose, having huge reserves of natural polymers, has been widely applied in pharmaceutical and biomedicine fields due to its good biocompatibility, biodegradability, non-toxicity and excellent mechanical properties. At present, water- resistant metal-based and petroleum-based materials applied in the medical field have obvious problems of poor biocompatibility and high cost. Therefore, water-resistant cellulose- based materials with good biocompatibility and low price have become an attractive alternative. This review aims to summarize the preparation of water-resistant cellulose- based materials and their potential application in pharmaceutical and biomedical in recent years. Common hydrophobic treatments of cellulose fibers or paper were overviewed. The preparation, properties and applications of water-resistant cellulose- based materials in the pharmaceutical and biomedical fields were summarized. Common hydrophobic treatments of cellulose fibers or paper were divided into chemical modification (graft polymerization, crosslinking, solution casting or dip-coating), physico-chemical surface modifications (plasma treatments, surface patterning, electrostatic spraying and electrowetting) and physical processing (electrostatic spinning, SAS process and 3D EHD printing). These hydrophobically processed cellulose fibers or paper could be prepared into various water-resistant cellulose-based materials and applied in pharmaceutical excipients, drug-loaded amphiphilic micelles, drug-loaded composite fibers, hydrophobic biocomposite film/coatings and paper-based detectors. They presented excellent water resistance and biocompatibility, low cytotoxicity and high drug loading ability, and stable drug release rate, etc., which could be used for water-insoluble drugs carriers, wound dressings, and medical testing equipment. Currently, water-resistant cellulose-based materials were mainly applied in water-insoluble drugs delivery carriers, wound dressing and medical diagnosis and presented great application prospects. However, the contradiction between hydrophobicity and mechanical properties of these reported water-resistant cellulose-based materials limited their wider application in biomedicine such as tissue engineering. In the future, attention will be focused on the higher hydrophobicity of water-resistant cellulose-based materials with excellent mechanical properties. In addition, clinical medical research of water-resistant cellulose-based materials should be strengthened.

Bistratal Au@Bi2S3 nanobones for excellent NIR-triggered/multimodal imaging-guided synergistic therapy for liver cancer

To fabricate a highly biocompatible nanoplatform enabling synergistic therapy and real-time imaging, novel Au@Bi2S3 core shell nanobones (NBs) (Au@Bi2S3 NBs) with Au nanorods as cores were synthesized. The combination of Au nanorods with Bi2S3 film made the Au@Bi2S3 NBs exhibit ultrahigh photothermal (PT) conversion efficiency, remarkable photoacoustic (PA) imaging and high computed tomography (CT) performance; these Au@Bi2S3 NBs thus are a promising nanotheranostic agent for PT/PA/CT imaging. Subsequently, poly(N-vinylpyrrolidone)-modified Au@Bi2S3 NBs (Au@Bi2S3-PVP NBs) were successfully loaded with the anticancer drug doxorubicin (DOX), and a satisfactory pH sensitive release profile was achieved, thus revealing the great potential of Au@Bi2S3-PVP NBs in chemotherapy as a drug carrier to deliver DOX into cancer cells. Both in vitro and in vivo investigations demonstrated that the Au@Bi2S3-PVP NBs possessed multiple desired features for cancer therapy, including extremely low toxicity, good biocompatibility, high drug loading ability, precise tumor targeting and effective accumulation. Highly efficient ablation of the human liver cancer cell HepG2 was achieved through Au@Bi2S3-PVP NB-mediated photothermal therapy (PTT). As both a contrast enhancement probe and therapeutic agent, Au@Bi2S3-PVP NBs provided outstanding NIR-triggered multi-modal PT/PA/CT imaging-guided PTT and effectively inhibited the growth of HepG2 liver cancer cells via synergistic chemo/PT therapy.

In situ assembly of Mt-HAP drug carrier with pH-responsive sustained release properties

The Mt-HAP composites were achieved by combining layered montmorillonite (Mt) and hydroxyapatite (HAP) nanoparticles produced by in situ assembly technique. Amoxicillin (AMX) loading and release experiment proved that the synthetic Mt-HAP composites demonstrated high drug loading ability and pH-responsive sustained release property. The AMX load of original Mt was 18.5 mg g−1, while that of Mt-HAP grew to 49.1 mg g−1. Experiments in simulated gastric fluid (pH 1.2) release indicated that Mt drug carrier having a higher release rate of AMX within the initial 2 h. But after that, the drug release rate of AMX from Mt-HAP has a greater value (about 65% over 12 h) than that of Mt (about 50% over 12 h) because of the dissolution of HAP under acidic circumstance. However, the cumulative sustained release rate of Mt-HAP in simulated intestinal fluid (pH 6.8) over 12 h was only 30%, and the drug release amount of Mt was still about 49%. Compared to Mt@AMX, the drug release rate of Mt-HAP @ AMX is sensitive to changes in pH. The findings claimed that the Mt-HAP composite exhibited extreme potential as a drug carrier for controllable drug delivery.

Multi-transformable nanocarrier with tumor extracellular acidity-activated charge reversal, size reduction and ligand reemergence for in vitro efficient doxorubicin loading and delivery.

Various nanoparticles as drug delivery system provide significant improvements in the cancer treatment. However, their clinical success remains elusive in large part due to their inability to overcome both systemic and tumor tissue barriers. The nanosystems with nanoproperty-transformability (surface, size, stability and target) hold great promise for achieving enhanced delivery efficacy. However, currently available systems that are mainly polymer-based assemblies usually suffer from the intrinsic drawbacks of poor stability, premature leakage and low drug loading as well as limited transformability. In this study, we designed a facile strategy to build a novel multi-transformable MSNs@GO nanosystem for efficient doxorubicin (DOX) loading and delivery. This novel nanosystem was well characterized and investigated in vitro. The results indicated that the MSNs@GO can realize a very high drug loading ability due to the large pore surface area of MSNs and the demonstrated donor-acceptor (boron‑nitrogen) coordination interactions between phenylboronic acid-containing nanocarriers and electron donor-containing DOX. More importantly, the novel nanocarriers can simultaneously achieve charge reversal, size reduction and ligand reemergence by shielding/deshielding transition via acid-cleavable dynamic boronate bonds under in vitro simulated acidic microenvironment of tumor tissues, opening a new avenue for improving delivery efficiency of chemotherapeutics.

Two-dimensional MXene/cobalt nanowire heterojunction for controlled drug delivery and chemo-photothermal therapy.

Two-dimensional (2D) MXene nanomaterials have explored as a great potential candidate for tumor therapy during recent decades, especially for photothermal therapeutic applications. However, MXene-based drug-carriers cannot be elaborately controlled in cancer therapy. To solve the problem, a heterostructured titanium carbide-cobalt nanowires (Ti3C2-CoNWs) nanocarrier is developed for synergetic anticancer with magnetic controlling ability, dual stimuli-responsive drug release, and chemo-photothermal therapy. The structure, drug loading/release behavior, magnetic controlling capacity, photothermal performance, and synergistic therapeutic efficiency of the Ti3C2-CoNWs nanocarrier heterojunction are investigated. The heterostructured Ti3C2-CoNWs nanocarrier exhibits excellent photothermal conversion efficiency under 808nm laser irradiation and high drug loading ability (225.05%). The doxorubicin (DOX) release behavior can be triggered by acid pH value (4-6) or near-infrared (NIR) irradiation. The Ti3C2-CoNWs nanocarrier heterojunction with synergistic chemo-photothermal therapeutic effect exhibits strong lethality for cancer cells than that of chemotherapy or photothermal therapy (PTT) alone. Therefore, Ti3C2-CoNWs nanocarrier heterojunction will be a promising choice for improving the efficiency of cancer treatment.

Fabrication of unimolecular micelle-based nanomedicines from hyperbranched polymers containing both terminal and internal reactive groups

Unimolecular micelles are an attractive type of nanocarriers for drug delivery, but developing unimolecular micelle-based nanomedicine with high drug loading capacity and excellent unimolecular stability is challenging. Herein, we report the design and synthesis of hyperbranched polymers containing both terminal and internal reactive groups for fabricating the unimolecular micelle-based nanocarriers with high drug loading ability and superior unimolecular stability using selective modification. Specifically, we synthesized hyperbranched poly(amino ester)s containing terminal acrylate groups and internal R groups (named HBPAE-R) via the Michael addition polymerization of A2 + BʹB2-R monomers, wherein A represents acrylate, and B, Bʹ represents the hydrogen in primary amine and secondary amine group, respectively, whereas R represents hydroxy, alkene or alkyne groups that do not participate in the polymerization process but assist in additional modification. Then, poly(ethylene glycol) (PEG) chains were linked to the surface of HBPAE-OH (representative molecules) with the subsequent conjugation of doxorubicin (DOX, representative drug) to the internal hydroxy groups through an acid-labile hydrazide bond, to afford anti-cancer drug-loaded hyperbranched star copolymers PEG-HBPAE-DOX. The obtained nanomedicines exhibited good unimolecular stability, relatively high drug loading content and a controlled drug release behavior. The in vitro cytotoxicity experiments further demonstrated the anti-tumor efficacy of these unimolecular nanomedicines. Our approach is expected to further boost research on the fabrication of multifunctional unimolecular nanomedicines from hyperbranched polymers containing both terminal and internal reactive groups.

PEG-amino acid-przewaquinone a conjugations: Synthesis, physicochemical properties and protective effect in a rat model of brain ischemia-reperfusion

A total of 21 PEG-przewaquinone A conjugations with high drug loading ability, good water solubility and in vivo slow-release quality were obtained by conjugating przewaquinone A with PEG through amino acids and tripeptides spacers respectively. Notably, compound 3a can obviously reduce the brain ischemia-reperfusion damage dose-dependently in a rat model, which indicated the efficacy of our PEG prodrug strategy.

Free Radicals: A Biocompatible Free Radical Nanogenerator with Real‐Time Monitoring Capability for High Performance Sequential Hypoxic Tumor Therapy (Adv. Funct. Mater. 39/2019)

In article number 1903436, Jinfeng Zhang, Chun-Sing Lee, and co-workers develop a biocompatible free radicals nanogenerator for efficient hypoxic tumor therapy. This nanosystem can produce cytotoxic free radicals under laser irradiation-induced hyperthermia in both normoxia and hypoxia to eradicate cancer cells. Meanwhile, a high drug loading ability and real-time drug release monitoring confers on the nanogenerator multifunctionality and high therapeutic performance.

A high-loading drug delivery system based on magnetic nanomaterials modified by hyperbranched phenylboronic acid for tumor-targeting treatment with pH response

To overcome the limited drug loading capacity of magnetic nanopharmaceuticals arising from the relatively large mass of the metal core, a high-loading drug delivery system based on amino-functionalized Fe3O4 magnetic nanospheres modified by hyperbranched phenylboronic acid (HPBA-Fe3O4) were prepared for the first time. The obtained nanomaterials were characterized by transmission electron microscopy, Fourier transform infrared, zeta potential, elemental analysis, vibrating sample magnetometry and X-ray diffraction analysis, and the results showed that hyperbranched phenylboronic acid (HPBA) were successfully grafted onto the surface of the magnetic nanospheres. The polymerization conditions, adsorption and desorption performance, and tumor-targeting ability of HPBA-Fe3O4 was investigated in detail through chemical and biological experiments. The drug loading amount and capacity of HPBA-Fe3O4 are 271.3 mg/g and 27.13%, respectively, which are 2.26 and 3.27 times greater than those of PBA-Fe3O4 and PEI-Fe3O4, and the thermodynamic fitting results further demonstrate the high drug loading ability of HPBA-Fe3O4. In vitro studies performed in U-87 MG malignant glioma cells and astrocytes via light and fluorescence microscopy analyses, cell counting kit-8 assays, and HPLC tests confirm the pH-sensitive release and tumor-targeted drug delivery capabilities of HPBA-Fe3O4. The facile fabrication of hyperbranched magnetic nanomaterials could be an alternative solution for designing high-loading, tumor cell-targeting and pH-responsive DDSs with high-mass cores.

Thermosensitive Nanogels with Cross-Linked Pd(II) Ions for Improving Therapeutic Effects on Platinum-Resistant Cancers via Intratumoral Formation of Hydrogels

Although bivalent palladium [Pd(II)] compounds exhibit favorable antitumor efficacy against platinum-resistant cancers, the mechanism remains unclear. Moreover, some drawbacks, such as structural lability, rapid elimination in vivo, and poor intratumoral retention, heavily limit their application in systemic tumor chemotherapy. Here, thermosensitive Pd-PNS nanogels are rationally designed by cross-linking coordination of Pd(II) ions with poly(styrenesulfonate-b-N-isopropylacrylamide-b-styrenesulfonate) (PNS), achieving high drug-loading ability (ca. 80% of entrapment efficiency and 40% of drug-loading efficiency), sustained release, and long-term retention of highly water-soluble K2PdCl4 in intratumoral administration. Cytotoxicity on sensitive/resistant MCF-7 cells and cancer stem cell (CSC) spheroids indicates that Pd-PNS nanogels could inhibit the palladium efflux of P-glycoprotein and multidrug resistance-associated protein-1 and thus enhance the DNA damage and toxicity of platinum-resistant MCF-7/Pt cells and their CSCs. Based on their temperature-sensitive sol–gel transition, Pd-PNS nanogels show sustained release profiles and long-term retention in tumors, further enhancing in vivo antitumor efficacy on MCF-7/Pt tumor-bearing BALB/c nude mice. Owing to these advantages of prolonged retention, efflux inhibition, and efficient CSCs killing ability, Pd-PNS nanogels are promising to be developed as a new temperature-sensitive delivery nanoplatform for injectable regional chemotherapy on platinum-resistant cancers.

Redispersible Pickering emulsion powder stabilized by nanocrystalline cellulose combining with cellulosic derivatives

The objective of this study is to use cellulose nanocrystals (CNC) combining with carboxymethyl cellulose sodium (CMC-Na) and hydroxypropyl methylcellulose (HPMC) as stabilizer to prepare novel redispersible camellia oil Pickering emulsions powder (CO-PEP). Cellulose nanocrystals modified with carboxymethyl cellulose sodium (CNCC) was prepared by homogenization technology. CNCC seemed to be rod-like particles with mean particle size of 124.2 ± 2.5 nm. And the cellulose structure, crystal state and thermal property of CNCC remained unchanged during the homogenization. The combination of CNC and CMC-Na in CNCC might be dependent of physical interaction. The mean particle size of optimum CO-PE/0.25%CNCC was 0.569 ± 0.023 μm. The CNCC based particle stabilizer might form the distinctive barrier layer around oil droplet. The redispersibility results demonstrated that 50% HPMC based CO-PEP formed large composite particle with high drug loading ability and exhibited superior redispersibility. Novel redispersible powdered Pickering emulsions could be prepared by cellulose nanocrystals combining with water-soluble cellulosic derivatives.

Metal-Organic Framework as a Microreactor for in Situ Fabrication of Multifunctional Nanocomposites for Photothermal-Chemotherapy of Tumors in Vivo.

Metal-organic frameworks (MOFs) have been applied in chemotherapeutic drug loading for cancer treatment, but challenging for cases with large and malignant lesions. To overcome these difficulties, combinational therapies of chemotherapy and photothermal therapy (PTT) with potentially high selectivity and slight aggressiveness have drawn tremendous attention to treat various tumors. However, current MOF-based nanohybrids with photothermal agents involve tedious synthesis processes and heterogeneous structures. Herein, we employ MIL-53 as a microreactor to grow polypyrrole (PPy) nanoparticles in situ for the fabrication of PPy@MIL-53 nanocomposites. Fe3+ in MIL-53, as an intrinsic oxidizing agent, can oxidize the pyrrole monomer to generate PPy nanoparticles. The prepared PPy@MIL-53 nanocomposites integrate the intrinsic advantages of MOFs with high drug loading ability and magnetic resonance imaging (MRI) capacity, and PPy nanoparticles with outstanding PTT ability and excellent biocompatibility. The versatile PPy@MIL-53 nanocomposites with multiple functions displayed in vitro and in vivo synergism of photothermal-chemotherapy for cancer, potentially MRI-guided. The proposed MOF microreactor-based synthesis strategy shows a promising prospect in the fabrication of diverse multifunctional nanohybrids for tumor theranostics in vivo.