Drug Carriers For Release Research Articles

Self-assembled mesoporous particles of Antheraea pernyi silk fibroin for encapsulation and sustained release of 5-fluorouracil

Mesoporous particles have attracted considerable attention in drug delivery system, because they can offer fast mass transport and overcome the diffusion restriction as occurred in micro/nano- porous particles. Conventional mesoporous particles are generally dominated by inorganic compounds, little concern has been raised over biodegradable organic polymers, especially silk fibroin. Here, we show that Antheraea pernyi (A. pernyi) silk fibroin, rich in Arg-Gly-Asp (RGD) moiety, can be developed into mesoporous particles via self-assembly in a direct and eco-friendly (without any organic solvents) manner for sustained release of 5-fluorouracil (5-FU). By cultivating a mild condition at 40 ℃, a mesoporous structure was successfully achieved without any foreign organic solvents. The self-assembled mesoporous particles were quasi-spherical in shape with an average diameter of 1.58 µm. Mesopores ran through the entire particles to construct a divergent structure with external pore diameters ranging from 30 to 60 nm and internal pore width of 6.225 nm. The mesoporous particles were predominated by β-sheet conformation (∼45%), which effectively reduced the weight-loss ratio to 2.6%. 5-FU was encapsulated into the mesoporous particles by hydrogen bonding and van der Waals force as well as ionic interactions. Drug loading efficiency and encapsulation efficiency were found to be 26.24% and 50.36%, respectively. The mesoporous particles enabled sustained drug release, with approximately 90% release after 110 h. After a small burst release (20%) of the surface-bound 5-FU, a slower linear release dominated by Fickian-diffusion occurred. These features together with the excellent biocompatibility of A. pernyi silk indicated that the self-assembled mesoporous particles would be an ideal carrier for sustained drug release to meet critical requirements of biomaterials. Furthermore, without any foreign materials, this one-step strategy may offer new green chemistry approaches as well as options to load bioactive drugs.

Fabrication of Electrospun PLA-nHAp Nanocomposite for Sustained Drug Release in Dental and Orthopedic Applications.

This study describes the fabrication of nanocomposites using electrospinning technique from poly lactic acid (PLA) and nano-hydroxyapatite (n-HAp). The prepared electrospun PLA-nHAP nanocomposite is intended to be used for drug delivery application. A hydrogen bond in between nHAp and PLA was confirmed by Fourier transform infrared (FT-IR) spectroscopy. Degradation study of the prepared electrospun PLA-nHAp nanocomposite was conducted for 30 days both in phosphate buffer solution (PBS) of pH 7.4 and deionized water. The degradation of the nanocomposite occurred faster in PBS in comparison to water. Cytotoxicity analysis was conducted on both Vero cells and BHK-21 cells and the survival percentage of both cells was found to be more than 95%, which indicates that the prepared nanocomposite is non-toxic and biocompatible. Gentamicin was loaded in the nanocomposite via an encapsulation process and the in vitro drug delivery process was investigated in phosphate buffer solution at different pHs. An initial burst release of the drug was observed from the nanocomposite after 1 to 2 weeks for all pH media. After that, a sustained drug release behavior was observed for the nanocomposite for 8 weeks with a release of 80%, 70% and 50% at pHs 5.5, 6.0 and 7.4, respectively. It can be suggested that the electrospun PLA-nHAp nanocomposite can be used as a potential antibacterial drug carrier for sustained drug release in dental and orthopedic sector.

Exopolysaccharides of Fungal Origin: Properties and Pharmaceutical Applications

Fungal exopolysaccharides (EPSs) represent an important group of bioactive compounds secreted by fungi. These biopolymers can be utilized individually or in combination with different bioactive substances for a broad range of pharmaceutical field applications, due to their various biological activities, such as antioxidant, antimicrobial, anti-inflammatory, antiviral, anti-diabetic, and anticoagulant effects. The paper presents an up-to-date review of the main fungal polysaccharides (pullulan, schizophyllan, scleroglucan, botryosphaeran, lentinan, grifolan, and lasiodiplodan), highlighting their structures, producing strains, and useful properties in a double position, as controlled release (rate and selectively targeting) drug carriers, but mostly as active immunomodulating and antitumor compounds in cancer therapy.

Cellulose based self-healing hydrogel through Boronic Ester connections for wound healing and antitumor applications

The application of biodegradable hydrogels in medical field has drawn great attention because their networked structure provided ideal spaces for drug loading and cell growth. In this research, the boronic acid was coupled onto carboxyethyl cellulose (CMC) to synthesize boronic acid grafted CMC (CMC-BA) conveniently and self-healing hydrogel was fabricated with polyvinyl alcohol (PVA) crosslinking through dynamic boronic ester bond. The CMC-BA/PVA hydrogel showed good biocompatibility and could be degraded by cellulase and in vivo. The hydrogel formed fast fit for localized injection to cover the irregular wounds and localize the antitumor drugs to the tumor site. The in vivo wound repairing experiment revealed the hydrogel could form airtight adhesion to the wound site to reduce blood loss and accelerate the wound repairing rate. The hydrogel as a drug release carrier also reduced the acute in vivo toxicity of DOX with antitumor performance well preserved through a controlled release profile. Based on the above advantages, the CMC-based hydrogel with boronic ester connection should have great potential in biomedical areas with profitable future.

Electro-stimulated drug release by methacrylated hyaluronic acid-based conductive hydrogel with enhanced mechanical properties

Recently, the design of stimuli-responsive hydrogels for controlled drug delivery systems has been extensively investigated to meet therapeutic needs and optimize the release pattern of the drug. Being a natural polyelectrolyte, hyaluronic acid (HA) is excellent potential to generate new opportunities for electro-responsive drug carrier applications. In the current study, HA-based electroconductive hydrogel was developed as a novel smart drug carrier for anti-inflammatory drug release by the combination of in-situ and post polymerization mechanisms. HA was modified through methacrylation reaction to introduce photocrosslinkable groups into its structure and then reduced graphene oxide (rGO) was encapsulated into methacrylated HA (HA/MA) hydrogel by using the photopolymerization technique. In the post polymerization process, polyaniline (PANI) was incorporated/loaded into HA/MA-rGO polymeric network produced in previous step. The produced HA/MA-rGO-PANI hydrogel exhibited sufficient electrical conductivity providing the desirable electro-responsive ability for Ibuprofen (IBU) release. Furthermore, it has superior mechanical performance compared to pure (HA/MA) and rGO containing (HA/MA-rGO) hydrogels. IBU release from the hydrogel was successfully triggered by electrical stimulation and the cumulative drug release also enhanced by increasing of the applied voltage. These results highlighted that the novel HA/MA-rGO-PANI hydrogel could be a promising candidate for electrical-stimulated anti-inflammatory release systems in neural implant applications.

Development and characterization of sodium alginate-g-poly(acrylic acid-co-2-acrylamido-2-methyl-1-propane sulfonic acid)/locust bean gum microbeads containing nickel ferrite nanoparticles for pH-responsive release of doxorubicin

The development of bioactive agent-loaded polymeric carriers offering pH-responsive has substantial potential value for biomedical applications. In light of this, we have designed pH-responsive polymeric microbeads as a vehicle for applications involving the drug delivery. At first, sodium alginate (SA) is grafted with acrylic acid and 2-acrylamido-2-methyl-1-propane sulfonic acid (AMPS) to generate SA-g-(AA-Co-AMPS). Next to functionalise NiFe2O4 nanoparticles with amino groups, nickel ferrite nanoparticles are treated with diethylene triamine and amine-nickel ferrite nanoparticles (ANiFe-NPs) are generated. Finally, we used the gelation ionic technique to develop microbeads using SA-g-(AA-Co-AMPS), locust bean gum (LBG), and ANiFe-NPs. By using FTIR, XRD, SEM, TEM, TGA, and DSC, the amino-nickel ferrite nanoparticles, SA-g-(AA-Co-AMPS), and microbeads were characterised. At pH 7.4 and 1.2, using doxorubicin (DOX) as a model agent in vitro drug release studies were conducted and the findings showed that the synthesized microbeads were proper for gastrointestinal drug administration. The developed microbeads were tested on MCF-7 cells and generated a considerable amount of reactive oxygen species (ROS), had a significant cytotoxicity effect on MCF-7 cells. The generated microbeads warrant further development and optimization to mediate pH-responsive drug release carriers.

Encapsulation of Imazalil in HKUST-1 with Versatile Antimicrobial Activity.

Based on high surface areas, adjustable porosity and microbicide activity, metal-organic frameworks (MOFs) HKUST-1 are widely used as drug release carriers for their slow degradation characteristics under slightly acidic conditions. In this work, porous HKUST-1 was reacted rapidly by cholinium salt (as the deprotonation agent and template) in an aqueous solution at room temperature. A novel antimicrobial system based on an imazalil encapsulated metal organic framework (imazalil IL-3@HKUST-1) was established. Imazalil IL-3@HKUST-1 could achieve synergism in inhibiting pathogenic fungi and bacteria. Moreover, six days after treatment, the slow and constant release of imazalil from imazalil IL@HKUST-1 exhibited better sustainability and microbicidal activity than imazalil. We believe that the method may provide a new strategy for related plant diseases caused by bacteria or fungi.

Application of G-quadruplex aptamer conjugated MSNs to deliver ampicillin for suppressing S. aureus biofilm on mice bone

Staphylococcus aureus is a common bacterial agent of biofilm formation in medical environments. The formed biofilm of this bacterium in bone tissue is one of the main causes of osteomyelitis, which is a serious health issue. Due to the importance of this infection after traumatic injuries or surgical intervention, it is necessary to develop a system that could release the antibiotics at the site of injury, specifically and gradually. The current study aimed to develop a nanosystem composed of single-stranded G-quadreplex DNA aptamer as the bio-recognition element, mesoporous silica nanoparticles (MSNs) as the carrier for gradual drug release, and Ampicillin as the cargo to be delivered to the site of infection. In silico methods were used to select an optimum binding aptamer against protein A of S. aureus . The binding of aptamer was confirmed via gel retardation assay, DLS, and Zeta potential analyses. The loading of the drug was confirmed by the FTIR method, and the drug release investigation showed almost 30 % of drug release via 48 h dialysis assay. The acquired results from the biofilm suppression assay indicated that this system provides a significant inhibitory effect against the S. aureus biofilm and has a high potential for the desired drug release to prevent the formation of biofilm, and could destroy the biofilm on the mice bone. The results of the MTT assay proved that this system does not pose a significant toxicity thread for MCF-7 cell viability, as a model for eukaryotic cells. In vivo studies are required to further confirm the efficacy of this system against S. aureus biofilm on bone.

Synthesis and characterization of gelatin/lignin hydrogels as quick release drug carriers for Ribavirin

In this study, hydrogels based on gelatin and lignin were fabricated as efficient drug carriers for Ribavirin. The obtained hydrogels were characterized by scanning electron microscopy (SEM), ATR-FTIR spectroscopy, differential scanning calorimetry (DSC), mechanical compression and rheometry. Results showed that the pore structure, viscoelastic behavior and swelling ability significantly influenced by varying lignin content and crosslinker ratio. By increasing the crosslinker N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) content, the pore size became smaller, while increasing the lignin content resulted in larger pores. In addition, all hydrogels show strong shear thinning behavior. Ribavirin was used as a drug model, and its release rate was enhanced by increasing lignin content in the binary hydrogel structure. A higher Ribavirin cumulative release was observed for gelatin/lignin with higher lignin content (3 %) hydrogel. These findings emphasize the chemical composition on the structure and the release behavior of lignin-containing hydrogels.

Development of polymeric microbeads-intercalated with montmorillonite nanoclay and silver nanoparticles for controlled release of levofloxacin, an antibacterial drug

Controlled release drug carriers have gained significant interest in recent years due to their potential to produce greater therapeutic success. To address this need, the study presents the fabrication of sodium alginate/poly(vinylpyrrolidone-co-vinyl acetate) microbeads intercalated with montmorillonite (MMT) clay and silver nanoparticles for the controlled release of levofloxacin by a simple ionotropic gelation technique. The prepared beads were characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (X-RD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) etc. The antibacterial activities of the synthesized microbeads were tested against Escherichia coli and Bacillus cereus by the agar disc diffusion method. The developed microbeads could significantly inhibit bacterial development. In vitro release studies and swelling studies were carried out at pH 7.4 simulated intestinal fluid and pH 1.2 simulated gastric fluid at 25 oC and 37 oC. The MMT-containing microbeads showed higher encapsulation efficiency and controlled drug release than other formulations. The results obtained from the swelling and in vitro release studies revealed that pH had influenced the drug release of developed microbeads and that they are suitable for intestinal drug delivery. The in vitro release kinetics was assessed by fitting the release data into the Korsmeyer- Peppas equation and finding that the release mechanism follows the Fickian diffusion process.

Effect of hydrophobic modification of block copolymers on the self-assembly, drug encapsulation and release behavior

In recent years, block copolymers together with their structure-property relationship in administrable drug delivery have attracted much concern. Three block copolymers BP123, BPF123 and H123 with the same PEO and PPO segments but different hydrophobic modification groups were synthesized. Commercial Pluronic block copolymers P123 was chosen for contrast. The effects of hydrophobic modification on the self-assembling behavior of the four copolymers were investigated via surface tension, transmission electron microscopy, steady state fluorescence and dynamic light scattering. With the enhancement of hydrophobicity, P123, BP123, BPF123 formed micelles and gradually decreased in critical aggregation concentrations (CAC) and size, while H123 formed vesicles. The dissolution and in vitro release capacities of the aggregates for the hydrophobic drug simvastatin were also evaluated. The stronger the hydrophobicity of copolymers, the stronger the drug solubilization ability for hydrophobic drug (H123 > BPF123 > BP123 > P123). Due to the enhancement of hydrophobicity, the tightly packed micelles formed by BP123 and BPF123, the drug release was slower. H123 had the highest solubility due to the closed bilayer vesicle structure and the interaction of hydrophobic groups with the drug, providing the slowest release rate. This study revealed that hydrophobic modification had a great impact on the self-assembly behavior of copolymers, modified copolymers can be applicable to sustained release drug carriers.

Hierarchical hollow monetite microspheres assembled with mesoporous nanosheets: Synthesis and applications in superior adsorbents for lead ions and pH-responsive release drug carrier

Hierarchical hollow monetite microspheres assembled with mesoporous nanosheets were firstly synthesized templating by both large and small micelles of mono-dodecyl phosphate. The obtained hollow monetite microspheres had a diameter of 10 ∼ 30 μm with a specific surface area of 86.76 m2 g−1 and a total pore volume of 0.466 cm3 g−1. The monetite nanosheets which were assembly units of the hollow microspheres possessed many mesopores with a pore size of about 25 nm. The mesoporous hollow monetite microspheres had adsorption capacity of lead ions and vancomycin as high as 1435.6 mg g−1 and 518 mg g−1, respectively. And the vancomycin loaded monetite microspheres exhibited a pH-responsive drug release behavior. The mesoporous hollow monetite microspheres have great potential in contaminants adsorbents and drug carriers.

Hydrogel beads based on carboxymethyl cassava starch/alginate enriched with MgFe2O4 nanoparticles for controlling drug release

Implementing novel oral drug delivery systems with controlled drug release behavior is valuable in cancer therapy. Herein, a green synthetic approach based on the sol-gel technique was adopted to prepare MgFe2O4 nanoparticles at different calcination temperatures using citric acid as a chelating/combustion agent. In this context, pH-responsive and magnetic carboxymethyl starch/alginate hydrogel beads (CMCS-SA) containing the MgFe2O4 nanoparticles were developed as potential drug carriers for the anticancer drug (Doxorubicin, Dox) release in simulated gastrointestinal fluids. Furthermore, in vitro release behaviors validated that these beads illustrated excellent stability in the simulated stomach liquids. In contrast, the data in simulated intestinal fluids showed sustained release of Dox because of their pH-sensitive swelling characteristics. Notably, applying an external magnetic field (EMF) could accelerate drug release from the beads. The in vitro release of drugs from gel beads was mainly accomplished by a combination of diffusion, swelling and erosion. Moreover, the cell cytotoxicity test and laser confocal results showed no harmful effects on normal cells (3T3) but were significant cytotoxic to colon cancer cell lines (HCT116) by drug-loaded hydrogel beads. Therefore, the prepared gel beads could be qualified as latent platforms for controlling the release of anticancer drugs in cancer treatment.

Fumarate‐co‐PEG‐co‐sebacate photopolymer and its evaluation as a drug release system

AbstractFumarate‐co‐PEG‐co‐sebacates with different fumaric/sebacic acid ratios are prepared by a simple thermal polycondensation reaction using p‐toluensulfonic acid as catalyst. These polymeric precursors are purified by washing with an appropriate organic solvent and the dried materials were photocured to yield elastic films under mild conditions. The properties of polymeric precursors and elastic materials are studied in detail and correlated with fumaric acid/sebacic acid ratios used in the thermal esterification reactions. It is shown that a higher amount of sebacic in the starting polymer leads to softer final film materials, with lower Tg and G' values, which also show higher degradation rates in vitro. Finally, the films are also evaluated as drug release carriers for in vitro release of Cephalexin and Progesterone. The results obtained in these studies indicate that the careful tailoring of the fumaric acid/sebacic acid ratio in the esterification reaction allows to finely tune the thermal, mechanical a degradation properties of the final cross‐linked elastic films.

Mechanistic insight into impact of clay on compressive elasticity of poly(N-alkyl acrylamide)/Laponite-based nanocomposite cryo-beads

Relationship between formation pathway and Hertzian elasticity of poly(N-isopropylacrylamide-co‑sodium acrylate)/Laponite® XLG, P(NIPA-NaA)/LAP, based nanocomposite cryo-beads was evaluated. Millimeter-sized nanocomposite cryo-beads were prepared by combination of dropwise freezing into cryogenic liquid (DFLC) method with sedimentation cryogelation method. pH-sensitive 3D-templete was formed by conducting free-radical crosslinking cryopolymerization of NIPA and NaA in the presence of synthetic hectorite Laponite® XLG as inorganic crosslinker and N,N′-methylenebis(acrylamide) as chemical crosslinker. The effects of network template, ionic comonomer, inorganic clay incorporation, pH- and ionic strength of swelling medium on the swelling and elasticity were evaluated as a function of bead size. The deformability of swollen cryo-beads was investigated using Hertzian elasticity. The crosslink density and Hertz modulus of nanocomposite beads vary with the droplet size and the polymer spheres with low crosslink density tend to absorb more water. In DFLC method, the desired sphere size and swelling can be adjusted by selecting the needle size used for dripping. The swelling degree increased significantly as the size of nanocomposite cryo-beads increased. At a fixed swelling ratio, the cylindrical nanocomposite cryogels exhibited greater elastic moduli and crosslink density than that of spherical gels. Correlation of elastic modulus of cryo-beads with swelling and cross-linked polymer concentration predicted a higher scaling exponent than the classical estimate for swelling in good solvents. It was investigated how the presence of 30 mol% pH-sensitive anionic comonomer NaA in the structure of all nanocomposite gels affects their pH-dependent swelling behavior. At pH < 5.7, the gels exhibited a lower swelling ratio, whereas at pH > 6.6 they tended to swell and followed second-order swelling kinetics by Fickian diffusion. When pH of swelling medium was alternately changed, all gels exhibited a pH-switch and swelling rate was two times higher than shrinkage rate. By investigating the effect of KCl, NaCl and K2CO3 on the swelling of cryobeads, it was determined how the salt cation changes the electrostatic repulsion between network charges. Nanocomposite cryo-beads showed fast pH-responsiveness and immediately reabsorbed the water they lost due to pH change, therefore, they can be designed as drug release carriers by pH-switching modulation.

Electrospun fibers as carriers for topical drug delivery and release in skin bandages and patches for atopic dermatitis treatment.

The skin is a complex layer system and the most important barrier between the environment and the organism. In this review, we describe some widespread skin problems, with a focus on eczema, which are affecting more and more people all over the world. Most of treatment methods for atopic dermatitis (AD) are focused on increasing skin moisture and protecting from bacterial infection and external irritation. Topical and transdermal treatments have specific requirements for drug delivery. Breathability, flexibility, good mechanical properties, biocompatibility, and efficacy are important for the patches used for skin. Up to today, electrospun fibers are mostly used for wound dressing. Their properties, however, meet the requirements for skin patches for the treatment of AD. Active agents can be incorporated into fibers by blending, coaxial or side-by-side electrospinning, and also by physical absorption post-processing. Drug release from the electrospun membranes is affected by drug and polymer properties and the technique used to combine them into the patch. We describe in detail the in vitro release mechanisms, parameters affecting the drug transport, and their kinetics, including theoretical approaches. In addition, we present the current research on skin patch design. This review summarizes the current extensive know-how on electrospun fibers as skin drug delivery systems, while underlining the advantages in their prospective use as patches for atopic dermatitis. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Design and evaluation of redox responsive disulfide containing resveratrol loaded nanocarrier anti-cancer activity in the MDA-MB-231 cell line

Redox-responsive resveratrol (RES)-loaded nanocarrier (R-NC) was fabricated using stearic acid-disulfide-methoxy poly (ethylene glycol) (SA-SS-mPEG) as a potential carrier for stimuli-responsive drug release. The synthesized redox responsive SA-SS-mPEG was evaluated through FTIR, 1H NMR, DTA/TGA and XRD analysis and was further utilized to develop R-NC by nanoprecipitation method. The NC was characterized for physicochemical properties and its susceptibility to redox and intracellular acidic pH were assessed through alterations in the size of the NC and release of resveratrol from the R-NC in the pH 5 & 7.4 medium with presence or absence of glutathione (GSH). The size of the NC was observed to increase from 140 nm to 1005 nm in the presence of an excessive concentration of GSH/pH 5 medium while showing lesser changes in the absence of GSH and pH 7.4. Drug release profiling of the R-NC confirmed that the presence of GSH in the pH 5 medium influenced the rapid release of the resveratrol by 89.23 ± 1.03% in 6 h compared to the GSH presence pH 7.4 (79.83 ± 1.15% in 6 h) and GSH free pH 5 & 7.4 medium respectively 59.67 ± 0.78% & 47.22 ± 1.18% in 18 h. R-NC, probably encompassed in cytotoxicity, reduces cancer cell proliferation with apoptotic regulation. Biocompatibility of the NC was confirmed through hemolytic assay, which showed that the NC deliberated safety up to the concentration of 200 µg/mL. Overall results accentuated the suitability of the developed R-NC for stimuli gated redox and pH-responsive drug delivery in the treatment of cancer.

Cell-Regulated Hollow Sulfur Nanospheres with Porous Shell: A Dual-Responsive Carrier for Sustained Drug Release

Cell-Regulated Hollow Sulfur Nanospheres with Porous Shell: A Dual-Responsive Carrier for Sustained Drug Release

Drug sustained release from degradable drug-loaded in-situ hydrogels in the posterior eye: A mechanistic model and analytical method

Biodegradable in-situ hydrogels as drug release carriers injected into the eye can treat Neovascular age-related macular degeneration (NV-AMD). Obviously, the biodegradation behavior of hydrogels affects the drug diffusion process in the eye, which can influence the drug concentration distribution and development in the macula. Herein, the intraocular diffusion process of the drugs which are released from the biodegradable hydrogel was studied by using finite element method, with the effect of the biodegradation behavior of hydrogels on the drug release process was considered. The effects of the initial average mesh size, rate constant of biodegradation, and position of hydrogels on the drug release process were analyzed. The results showed that the biodegradation behavior of hydrogels decreases the drug release rate by gradually expanding the mesh size, prolonging the duration of drug treatment in the macula. The biodegradable hydrogels’ position, initial mesh size, and biodegradation rate constant also affect drug delivery. Different locations of hydrogels denote different distances between the drug and macula, which affects the diffusion time and further influence the macular drug concentration. The initial mesh size alters the initial drug release rate, which affects the duration of hydrogels’ drug release process and drug concentration and duration in the macula. The hydrogel degradation rate affects the development of its mesh size, which affects the drug diffusion in hydrogels, and further affects the drug concentration in the macular region.

Acid-Degradable Hydrogen-Generating Metal-Organic Framework for Overcoming Cancer Resistance/Metastasis and Off-Target Side Effects.

The development of stimuli‐responsively degradable porous carriers for both controlled drug release and high biosafety is vitally important to their clinical translation, but still challenging at present. A new type of porphyrin–iron metal organic framework (Fe‐MOF) nanocrystals is engineered here as acid‐degradable drug carrier and hydrogen donor by the coordination between porphyrin and zero‐valence Fe atom. Fe‐MOF nanocrystals exhibit excellent acid‐responsive degradation for H2 generation and simultaneous release of the loaded drug for combined hydrogen‐chemotherapy of cancer multidrug resistance (MDR) and metastasis and for local hydrogen eradication of the off‐target induced toxic side effects of the drug to normal cells/tissues. Mechanistically, released H2 assists chemotherapeutic drug to efficiently inhibit cancer metastasis by immunoactivating intratumoral M1‐phenotype macrophages and consequently downregulating the expression of metastasis‐related matrix metalloproteinase‐2 (MMP‐2) and can also downregulate the expressions of both P‐glycoprotein (P‐gp) protein and adenosine triphosphate (ATP) in MDR cancer cells to sensitize chemotherapeutic drug for enhanced damage to mitochondria and DNA. High anti‐MDR/antimetastasis efficacies and high biocompatibility endow Fe‐MOF nanocrystals and the Fe‐MOF‐based nanomedicine with high potential for clinical translation.