pH-responsive Drug Release Behavior Research Articles

Cetuximab functionalized chitosan/hyaluronic acid-based nanoparticles loaded with cabazitaxel enhances anti-tumor efficacy in DMBA-induced breast cancer model in rats through spatial targeting

The article discusses the ionic gelation of cationic chitosan (CS) with anionic hyaluronic acid (HA) sodium salt to form nanoparticles in the range of 125 nm. The particles were further functionalized with cetuximab to endow it with the ability to spatially target the tumor over-expressing EGFR. Solid-state characterization of the particles using XRD, FTIR, and DSC revealed the formation of stable nanoparticles with Cabazitaxel loaded in the amorphous nanostructure. XPS study used to assess the surface characteristics indicated that the cetuximab was successfully anchored on the surface of the particle. The prepared CS-HA-Cmab-NP elicited a pH-responsive drug release behavior due to the presence of CS in the matrix. In vitro performance of the nanoparticles was evaluated on MDA-MB-231 breast cancer cell lines showed overall increase in efficacy. In vivo pharmacokinetic and anti-tumor effect evaluated in female Sprague Dawley rats indicated that the Cmab-conjugated nanoparticles improved half-life of cabazitaxel and tumor reduction capability with higher survival rate and lower reduction in body weight. The results indicate that CS/HA nanoparticles anchored with cetuximab show enhanced efficacy in reducing the breast cancer tumor in DMBA-induced breast tumor model through spatial targeting, consequently reducing the systemic toxicity.

Dynamic Covalent Boronic-Acid-Functionalized Alginate/PVA Hydrogels for pH and Shear-Responsive Drug Delivery.

Herein, we investigated hydrogels composed of boronic-acid-functionalized alginate and blended with polyvinyl alcohol (PVA) of different molecular weights to control the release of metoclopramide hydrochloride as a function of pH and shear stress. The functionalization of alginate introduced dynamic covalent bonding and pH-responsive properties that can modulate network connectivity. The study investigated the viscoelastic properties of the hydrogels, their drug release profiles, and their responsiveness to changes in pH and shear forces. The results showed that a higher PVA molecular weight and alkaline pH conditions increased hydrogel viscosity and stiffness due to a more stable and interconnected network structure than acidic pH. Metoclopramide release revealed that the hydrogels exhibited pH-responsive drug release behavior. The drug was more readily released under acidic conditions due to the instability of sp2-hybridized boronate ester bonds. The influence of shear forces on the release of metoclopramide was also investigated at shear rates of 1, 10, and 100 s-1, revealing their effect on matrix stiffening. Research shows that AlgBA/PVA hydrogels have unique properties, such as dynamic covalent bonding, that make them sensitive to external mechanical forces. This sensitivity makes them ideal for applications where physiological conditions trigger drug release.

Acidic/hypoxia dual-alleviated nanoregulators for enhanced treatment of tumor chemo-immunotherapy

Chemotherapy plays a crucial role in triple-negative breast cancer (TNBC) treatment as it not only directly kills cancer cells but also induces immunogenic cell death. However, the chemotherapeutic efficacy was strongly restricted by the acidic and hypoxic tumor environment. Herein, we have successfully formulated PLGA-based nanoparticles concurrently loaded with doxorubicin (DOX), hemoglobin (Hb) and CaCO3 by a CaCO3-assisted emulsion method, aiming at the effective treatment of TNBC. We found that the obtained nanomedicine (DHCaNPs) exhibited effective drug encapsulation and pH-responsive drug release behavior. Moreover, DHCaNPs demonstrated robust capabilities in neutralizing protons and oxygen transport. Consequently, DHCaNPs could not only serve as oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment (TME) by depleting lactic acid, thereby effectively overcoming the resistance to chemotherapy. Furthermore, DHCaNPs demonstrated a notable ability to enhance antitumor immune responses by increasing the frequency of tumor-infiltrating effector lymphocytes and reducing the frequency of various immune-suppressive cells, therefore exhibiting a superior efficacy in suppressing tumor growth and metastasis when combined with anti-PD-L1 (αPD-L1) immunotherapy. In summary, this study highlights that DHCaNPs could effectively attenuate the acidic and hypoxic TME, offering a promising strategy to figure out an enhanced chemo-immunotherapy to benefit TNBC patients.

The preparation of pH-sensitive doxorubicin prodrug for enhanced antitumor efficacy

We have produced a micelle nanoparticle with intrinsic pH response, which is formed by self-assembled amphiphilic polyethylene glycol-Schiff-doxorubicin (PEG-Schiff-DOX) prodrug. These nanoparticles can maintain stability well under normal conditions and last for more than a week, but they will rapidly decompose in slightly acidic environments. The concentration of DOX in the nano solution is high with the drug loading ratio of 49.4%. This pH-responsive drug release behavior may lead to higher intracellular drug concentrations and prolonged action times. CCK-8 assays have shown that the nanosuspension exhibits superior anti-tumor activity against HeLa cells compared to free DOX. It is believed that these nanoparticle-based prodrug have great potential for developing DOX formulations for cancer therapy.

Biodegradable pectin-based thermo-responsive composite GO/hydrogel with mussel inspired tissue adhesion for NIR enhanced burn wound healing

Thermo-responsive hydrogels with biodegradability have great application in biomedical areas, while the Poly(N-isopropylacrylamide) (PNIPAM) based hydrogels exhibiting lower critical solution temperature (LCST) around body temperature have shown promising applications in diverse areas such as drug delivery, tissue engineering, and wound repairing. In this study, PNIPAM based thermo-responsive copolymer with ketone functional group was polymerized and the LCST was regulated to body temperature, then biodegradable self-healing hydrogels with injectability were fabricated by cross-linking the thermo-responsive copolymers with dopamine functionalized pectin hydrazide (PDAH). The hydrogel exhibited good mechanical strength, excellent biocompatibility and thermo-responsive sustained drug release process. The nano-graphene oxide (GO) was incorporated to design near-infrared (NIR) sensitive nanocomposite hydrogel to serve as photothermal enhanced wound dressing with vancomycin loading. The composite hydrogel also showed pH-responsive drug release behavior and the NIR irradiation also accelerated the release rate based on photothermal induced phase transition. More importantly, the nanocomposite hydrogel with vancomycin loading and photothermal property can promoted burn wound repairing rate by inhibiting the bacterial growth. As a result, this GO composite hydrogel (GO/hydrogel) could act as NIR triggered photo-thermal enhanced drug delivery platform for promoted wound repairing in the near future.

Hyaluronic acid-engineered Bcl-2 inhibitor nanocrystals for site-specific delivery to breast tumor cells.

Aim: This investigation aims to repurpose venetoclax using hyaluronic acid-coated venetoclax nanocrystals (HA-VEN-NCs) to target breast cancer. Materials & methods: An antisolvent precipitation method was used to fabricate the nanocrystals and optimize them using central composite design. Hyaluronic acid (HA)-coated and -uncoated nanocrystals were compared in terms of in vitro drug release, cell line studies, CD44-expressing breast tumor cell binding capability and anticancer activity. Results: HA-VEN-NCs and venetoclax nanocrystals (VEN-NCs) showed pH-responsive drug-release behavior, exhibiting sustained release at pH 6.8. Our extensive in vitro cell line investigation showed that HA-VEN-NCs efficiently bind to CD44-expressing breast tumor cells and possess excellent anticancer activity (half maximal inhibitory concentration: 2.00μg/ml) compared with VEN-NCs. Conclusion: Our findings anticipate that HA-VEN-NCs could serve as valuable nanoplatforms for cancer treatments in the future.

Thermosensitive Polymer-Modified Mesoporous Silica for pH and Temperature-Responsive Drug Delivery

A mesoporous silica-based drug delivery system (MS@PNIPAm-PAAm NPs) was synthesized by conjugating the PNIPAm-PAAm copolymer onto the mesoporous silica (MS) surface as a gatekeeper that responds to temperature and pH changes. The drug delivery studies are carried out in vitro at different pH (7.4, 6.5, and 5.0) and temperatures (such as 25 °C and 42 °C, respectively). The surface conjugated copolymer (PNIPAm-PAAm) acts as a gatekeeper below the lower critical solution temperature (LCST) (<32 °C) and as a collapsed globule structure above LCST (>32 °C), resulting in controlled drug delivery from the MS@PNIPAm-PAAm system. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cellular internalization results support the prepared MS@PNIPAm-PAAm NPs being biocompatible and readily taken up by MDA-MB-231 cells. The prepared MS@PNIPAm-PAAm NPs, with their pH-responsive drug release behavior and good biocompatibility, could be used as a drug delivery vehicle where sustained drug release at higher temperatures is required.

Monodisperse CaCO3-loaded gelatin microspheres for reversing lactic acid-induced chemotherapy resistance during TACE treatment

Transarterial chemoembolization (TACE) is an important approach for the treatment of unresectable hepatocellular carcinoma (HCC). However, the lactic acid-induced acidic tumor microenvironment (TME) may reduce the therapeutic outcome of TACE. Herein, monodispersed gelatin microspheres loaded with calcium carbonate nanoparticles (CaNPs@Gel-MS) as novel embolic agents were prepared by a simplified microfluidic device. It was found that the particle size and homogeneity of as-prepared CaNPs@Gel-MS were strongly dependent on the flow rates of continuous and dispersed phases, and the inner diameter of syringe needle. The introduction of CaNPs provided the gelatin microspheres with an enhanced ability to encapsulate the chemotherapeutic drug of DOX, as well as a pH-responsive sustained drug release behavior. In vitro results revealed that CaNPs@Gel-MS could largely increase the cellular uptake and chemotoxicity of DOX by neutralizing the lactic acid in the culture medium. In addition, CaNPs@Gel-MS exhibited an excellent and persistent embolic efficiency in a rabbit renal model. Finally, we found that TACE treatment with DOX-loaded CaNPs@Gel-MS (DOX/CaNPs@Gel-MS) had a much stronger ability to inhibit tumor growth than the DOX-loaded gelatin microspheres without CaNPs (DOX@Gel-MS). Overall, CaNPs@Gel-MS could be a promising embolic microsphere that can significantly improve anti-HCC ability by reversing lactic acid-induced chemotherapy resistance during TACE treatment.

Synthesis of rifaximin-loaded ZnO@ZIF-8 nanocomposites for Staphylococcal biofilm eradication and related infection therapy

Rifaximin-loaded ZnO@ZIF-8 nanocomposites, with a positive zeta potential, pH-responsive drug release behavior and self-antibacterial activity, show great potential for anti-biofilm application.

Fabrication and properties of multi-functional polydopamine coated Cu/F-codoped hydroxyapatite hollow microspheres as drug carriers

Due to its excellent bone conductivity and drug adsorption as well as pH-responsive drug release property, hydroxyapatite (HAp) is widely used as a drug carrier in bone repair field. Here, we report for the first time a novel multi-functional polydopamine (PDA) coated Cu/F-codoped HAp (Cu/F-HAp-PDA) hollow microspheres. Both Cu2+ and F- were successfully doped into the lattice of HAp and uniformly distributed in the shell of hollow microspheres through a one-step hydrothermal synthesis. Then PDA was coated homogeneously on the outer layer of Cu/F-HAp hollow microspheres. Both Cu/F-HAp and Cu/F-HAp-PDA samples displayed high drug loading efficiency and pH responsive drug release behavior. Moreover, the obtained Cu/F-HAp-PDA hollow microspheres exhibited excellent photothermal conversion efficiency and photothermal stability. The molecular dynamics simulations showed that PDA and HAp can form mutual binding mainly through Ca-O bonding, while doxorubicin (DOX) is mainly bound to PDA molecules through hydrogen bonding and π-π stacking interaction.

Mesoporous silica (SBA-15) with enriched amidoxime functionalities for pH-controlled anticancer drug delivery

Amidoxime (AMI), an amphoteric functional ligand, mesoporous silica material (SBA-15@AMI NPs) was prepared and the pH-responsive drug release behavior was examined using Dox as model anticancer drug. Further, the cytocompatibility and the cell uptake results revealed that SBA-15@AMI NPs could be applied as pH-responsive drug delivery applications in cancer therapy. • Developing pH- responsive drug delivery system is attracted a great concern. • An amphoteric ligand functionalized SBA-15@AMI NPs for pH-responsive drug delivery system has been proposed. • The SBA-15@AMI NPs is applicable for delivery of anticancer drugs in cancer therapy. Amidoxime (AMI) functionalized mesoporous silica material (SBA-15@AMI NPs) was synthesized by surface modification approaches. This method allows for the creation of a higher concentration of amidoxime ligand groups to the SBA-15's surface without affecting the morphology. The synthesized SBA-15@AMI NPs were verified using a range of instrumental characterizations. Further, the drug loading and pH-responsive release behavior of the SBA-15@AMI NPs were examined using Dox as model anticancer drug. The biocompatibility and cellular uptake behavior was studied using MCF-7 cell line. Overall, the prepared SBA-15@AMI NPs could be applied as pH-responsive drug delivery applications in cancer therapy.

Novel pH-responsive and mucoadhesive chitosan-based nanoparticles for oral delivery of low molecular weight heparin with enhanced bioavailability and anticoagulant effect

Low molecular weight heparin (LMWH) shows great anticoagulant effect for prevention and treatment of deep venous thrombosis. However, its oral administration is seriously hindered by multiple obstacles. In this study, a pH-responsive delivery system was developed to protect LMWH from gastrointestinal tract degradation and facilitate its absorption across gastrointestinal mucosa. The LMWH-loaded nanoparticles (pH-TCS/O-CMCS@LMWH) were prepared by ionic-crosslinking reaction between positive-charged amino groups of thiolated chitosan (TCS) as well as o-carboxymethyl chitosan (O-CMCS) and oppositely charged HP55. As a result, the prepared nanoparticles proved to spherical shape with an average size of 332 nm, high encapsulation efficiency of 96.6% and drug-loading content of 12.04 IU/mg. The proposed pH-TCS/O-CMCS@LMWH also showed good colloidal stability, potential mucoadhesive effect and desirable pH-responsive drug release behavior, which decreased pre-mature LMWH release in acidic environment but increase its targeted release in intestine environment. After oral administration, the pH-TCS/O-CMCS@LMWH shown enhanced bioavailability and significant antithrombotic effect in a rat model of venous thrombosis. In conclusion, pH-TCS/O-CMCS nanoparticles can be successfully hold great promising for oral administration of LMWH and potential treatment for thrombosis.

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.

Lead/cadmium-free near-infrared multifunctional nanoplatform for deep-tissue bimodal imaging and drug delivery

Well-designed multifunctional nanoplatforms integrating diagnosis and therapy capabilities are of significant importance in the emerging research area of theranostics, which is expected to have great impact on future medicine. Herein, we rationally designed and engineered a multifunctional NaGdF4:Nd3+@mSiO2 nanoplatform by loading ultrasmall NaGdF4:Nd3+ nanoparticles (∼4.1 nm in diameter) into relatively large-channel mesoporous SiO2 (mSiO2) nanospheres for the first time. Thanks to the unique combination of paramagnetic property, and the capability of being excited by near infrared (NIR) light in the first biological window (NIR-I: 700–950 nm) and emitting in the second biological window (NIR-II: 1000–1350 nm) in single-type nanoparticles of NaGdF4:Nd3+, the NaGdF4:Nd3+@mSiO2 nanoplatform realizes magnetic resonance and NIR photoluminescence dual-mode tumor imaging of live mice. In particular, this NIR-I excitation and NIR-II emission property enables in vitro NIR porcine tissue photoluminescence imaging up to 12 mm in thickness. Moreover, the unique three-dimensional mesoporous structure of the nanoplatform allows the efficient loading of doxorubicin molecules (DOX, a commonly used drug model) at a high level and demonstrates pH-responsive drug release behavior that is beneficial for cancer-targeted therapy. More importantly, this NIR-II emitting nanoplatform does not contain toxic heavy metals of lead (Pb) and cadmium (Cd) usually found in NIR-emitting nanoparticles and further, comprises a highly biocompatible, protective SiO2 network. As a result, the NaGdF4:Nd3+@mSiO2 nanoplatform demonstrates much less cytotoxicity, as compared to the counterpart containing Pb and/or Cd-based quantum dots. All these features endow the multifunctional NaGdF4:Nd3+@mSiO2 nanoplatform great potential in simultaneous disease imaging diagnostics and therapeutics.

One-pot self-assembly fabrication of chitosan coated hollow sphere for pH/ glutathione dual responsive drug delivery

Chitosan-coated poly (methacrylic acid) (PMAA) hollow spheres with 64 ± 3% drug loading capacity and low drug leakage (7 ± 2%, 54 h) were prepared through a novel one-pot two-step self-assembly process. Site-specific doxorubicin (DOX) loading and chitosan coating were achieved by electrostatic interaction to fulfill efficient drug loading and well-controlled drug release behavior. In vitro drug release profile revealed the pH and glutathione (GSH) dual responsive fast triggered drug release behavior, reaching 62 ± 3% during the first 10 h. And completely drug release could be achieved in 54 h. The high drug content and sensitive tumor microenvironment responsibility lead to similar anti-cancer efficiency with free doxorubicin in in vitro MTT assay. This self-assembly guided one-pot two-step fabrication process was proved to be an effective and convenient way to prepare the well-defined multi-layer structure and might be further employed in fabricating high-performance drug delivery systems.

Preparation and functional study of pH-sensitive amorphous calcium phosphate nanocarriers

Schematic presentation of synthetic procedure of HA-FCNs (a) and HA-FCNs/ACP (b). • The great prospects in cancer treatment of multifunctional nanoparticles. • pH responsive drug release behavior and excellent biocompatibility. • Targeted into human lung cancer cells (A549 cells). • Stronger fluorescence signals. Recently, multifunctional nanoparticles have shown great prospects in cancer treatment, which have the ability to simultaneously deliver the drug, image and target tumor cells. In this paper, we designed a luminescent nanoparticles platform based on hydrothermal hyaluronic acid/amorphous calcium phosphate (HA-FCNs/ACP) with multifunctional properties for drug delivery, bio-imaging, and targeting treatment. HA-FCNs/ACP shows an ability to load curcumin (Cur) with pH-sensitive responsive drug release behavior and excellent biocompatibility. HA-FCNs/ACP dispersed in the cytoplasm through the overexpressed CD44 receptor that is actively targeted into human lung cancer cells (A549 cells). Meanwhile, the viability of A549 cells was significantly inhibited in vitro . The prepared HA-FCNs and HA-FCNs/ACP both exhibit excellent targeted bioimaging performance on cancer cells. Hence, the as-prepared nanoparticles have promising applications in treating tumor disease.

Dual-targeting magnetic fluorescent mesoporous organosilicon hollow nanospheres for gambogic acid loading, sustained release and anti-tumor properties

Hydrophilic mesoporous organosilica nanoparticles (HMNPs) were synthesized by introducing Fe3O4 on the basis of mesoporous organosilicon nanoparticle hollow spheres as a drug carrier. N- and S- doped graphene quantum dots (NS-GQDs) and polyethylenimine (PEI) were grafted onto the surface of HMNPs. Finally, two types of composite mesoporous particles, HMNPs-NS-GQDs-PEI-HA and HMNPs-NS-GQDs-PEI-FA which can enter VX2 cells for fluorescence confocal imaging, were further modified by targeting ligand hyaluronic acid (HA) and folic acid (FA). The heteroatoms of NS-GQDs have intelligent functional effects, which can not only improve the photoluminescence performance of GQDs, but also generate conjugated quantum dots with GA, so as to synergistically improve the drug effectiveness. Under illumination by near-infrared (NIR) radiation, gambogic acid (GA)-loaded HMNPs was promoted to the sustained release of gambogic acid. The loading and sustained release of the anticancer drug GA on the compound mesoporous particles were studied. The cytotoxicity and antitumor properties of the compound mesoporous particles were investigated by both in vitro cell experiments and in vivo experiments in mice. The results showed that HMNPs-NS-GQDs-PEI-HA and HMNPs-NS-GQDs-PEI-FA have desired fluorescence and magnetic properties for cell fluorescence imaging and magnetic targeting of cancer cells. Both of composite mesoporous particles have desired loading capacity on GA and pH-responsive drug release behavior as well as low cytotoxicity and good biocompatibility. The cell survival rate of HMNPs-NS-GQDs-PEI-HA and HMNPs-NS-GQDs-PEI-FA loaded with GA was only 7.69% and 8.71%, respectively, after 24 h, which can effectively induce the apoptosis of VX2 cells. Tumor experiments in mice demonstrated that HMNPs-NS-GQDs-PEI-HA inhibits tumor growth and exhibits magnetic targeting function.

A cellulose nanofibril-reinforced hydrogel with robust mechanical, self-healing, pH-responsive and antibacterial characteristics for wound dressing applications

BackgroundBacterial infection in wounds has become a major threat to human life and health. With the growth use of synthetic antibiotics and the elevated evolution of drug resistant bacteria in human body cells requires the development of novel wound curing strategies. Herein, a novel pH-responsive hydrogel (RPC/PB) was fabricated using poly(vinyl alcohol)-borax (PB) and natural antibiotic resveratrol grafted cellulose nanofibrils (RPC) for bacterial-infected wound management.ResultsIn this hydrogel matrix, RPC conjugate was interpenetrated in the PB network to form a semi-interpenetrating network that exhibited robust mechanical properties (fracture strength of 149.6 kPa), high self-healing efficiency (> 90%), and excellent adhesion performance (tissue shear stress of 54.2 kPa). Interestingly, the induced RPC/PB hydrogel showed pH-responsive drug release behavior, the cumulative release amount of resveratrol in pH 5.4 was 2.33 times than that of pH 7.4, which was adapted well to the acidic wound microenvironment. Additionally, this RPC/PB hydrogel exhibited excellent biocompatibility and antioxidant effect. Moreover, in vitro and in vivo results revealed that such RPC/PB hydrogel had excellent antibacterial, skin tissue regeneration and wound closure capabilities.ConclusionTherefore, the generated RPC/PB hydrogel could be an excellent wound dressing for bacteria-infected wound healing.

Synthesis and Characterization of Tetracycline Loaded Methionine-Coated NiFe2O4 Nanoparticles for Anticancer and Antibacterial Applications.

In the present study, nickel ferrite (NiFe2O4)-based smart magnetic nanoparticles were fabricated and coated with methionine. Physiochemical characterization of the obtained Met-NiFe2O4 nanoparticles revealed the presence of methionine coating over the nanoparticle surface. Drug release study indicated that Tet-Met-NiFe2O4 nanoparticles possess pH-responsive controlled drug release behavior for tetracycline (Tet). The drug loading content for Tet was found to be 0.27 mg/L of nanoparticles. In vitro cytotoxicity test showed that the Met-NiFe2O4 nanoparticles is biocompatible. Moreover, this magnetic nanostructured material shown strong anticancer property as these nanomaterials significantly reduced the viability of A375 cells when compared to free Tet solution. In addition, Tet-Met-NiFe2O4 nanoparticles also showed strong antibacterial activity against different bacterial pathogens.

Scalable Manufacture of Curcumin-Loaded Chitosan Nanocomplex for pH-Responsive Delivery by Coordination-Driven Flash Nanocomplexation.

Metal coordination-driven nanocomplexes are known to be responsive to physiologically relevant stimuli such as pH, redox, temperature or light, making them well-suited for antitumor drug delivery. The ever-growing demand for such nanocomplexes necessitates the design of a scalable approach for their production. In this study, we demonstrate a novel coordination self-assembly strategy, termed flash nanocomplexation (FNC), which is rapid and efficient for the fabrication of drug-loaded nanoparticles (NPs) in a continuous manner. Based on this strategy, biocompatible chitosan (CS) and Cu2+ can be regarded anchors to moor the antitumor drug (curcumin, Cur) through coordination, resulting in curcumin-loaded chitosan nanocomplex (Cur-loaded CS nanocomplex) with a narrow size distribution (PDI < 0.124) and high drug loading (up to 41.75%). Owing to the excellent stability of Cur-loaded CS nanocomplex at neutral conditions (>50 days), premature Cur leakage was limited to lower than 1.5%, and pH-responsive drug release behavior was realized in acidic tumor microenvironments. An upscaled manufacture of Cur-loaded CS nanocomplex is demonstrated with continuous FNC, which shows an unprecedented method toward practical applications of nanomedicine for tumor therapy. Furthermore, intracellular uptake study and cytotoxicity experiments toward H1299 cells demonstrates the satisfied anticancer efficacy of the Cur-loaded CS nanocomplex. These results confirm that coordination-driven FNC is an effective method that enables the rapid and scalable fabrication of antitumor drugs.