pH-responsive Polymer Research Articles

Multicyclic topology-enhanced micelle stability and pH-sensitivity

Cyclic polymers have been reported to show unique properties and often better performance than linear analogues due to the absence of polymer chain ends, therefore great efforts have been devoted to the development of various cyclic polymers for biomedical applications. However, the effect of multicyclic topology on the stimuli-responsiveness of polymers has not been elucidated so far, to our knowledge, likely due to the lack of an efficient and powerful strategy for the controlled preparation of multicyclic polymers with well-defined structures and compositions. Clarification of this structure–property relationship will not only contribute to the rational design and development of novel cyclic polymer-derived materials with better properties for biomedical applications, but also promote greatly the clinical translations of these cyclic topology-based materials. A panel of amphiphilic pH-responsive multicyclic polymers (MCPs) were prepared via reversible addition-fragmentation chain-transfer (RAFT) copolymerization of a cyclic macromonomer, poly(oligoethylene glycol methacrylate) (M−cPOEGMA) and N,N-dimethyl aminoethyl methacrylate (DMAEMA). The effect of multicyclic topology on the colloidal stability and stimuli-responsiveness of the resulting self-assembled micelles was investigated in detail. Interestingly, MCP1 micelles with a polymer composition of P(DMAEMA50-st-(M−cPOEGMA7)3) showed much greater stability with a CMC value as low as 130.5 nM and more complete acidic pH-triggered disassembly than the single cyclic polymers (SCPs)-based micelle counterparts, which further endows the doxorubicin (DOX)-loaded MCP1 micelles with an approximately twofold lower IC50 value (greater in vitro cytotoxicity) than that of the SCP-based analogues. This study therefore highlights for the first time the incorporation of multicyclic topology as a useful and efficient alternative to the simultaneously enhanced colloidal stability and stimuli-responsiveness of polymeric self-assemblies for controlled release application.

Rapid Ultratough Topological Tissue Adhesives.

Tissue adhesives capable of achieving strong and tough adhesion in permeable wet environments are useful in many biomedical applications. However, adhesion generated through covalent bond formation directly with the functional groups of tissues (i.e., COOH and NH2 groups in collagen), or using non-covalent interactions can both be limited by weak, unstable, or slow adhesion. Here, it is shown that by combining pH-responsive bridging chitosan polymer chains and a tough hydrogel dissipative matrix one can achieve unprecedented ultratough adhesion to tissues (>2000Jm-2 ) in 5-10min without covalent bond formation. The strong non-covalent adhesion is shown to be stable under physiologically relevant conditions and strongly influenced by chitosan molecular weight, molecular weight of polymers in the matrix, and pH. The adhesion mechanism relies primarily on the topological entanglement between the chitosan chains and the permeable adherends. To further expand the applicability of the adhesives, adhesion time can be decreased by dehydrating the hydrogel matrix to facilitate rapid chitosan interpenetration and entanglement (>1000Jm-2 in ≤1min). The unprecedented adhesive properties presented in this study open opportunities for new strategies in the development of non-covalent tissue adhesives and numerous bioapplications.

Nucleus-specific RNAi nanoplatform for targeted regulation of nuclear lncRNA function and effective cancer therapy.

In the context of cancer therapy, a recently identified therapeutic target is represented by the essential subtype of RNA transcripts - the long noncoding RNAs (lncRNA). While this is the case, it is especially difficult to successfully regulate the expression of this subtype in vivo, particularly due to the protection granted by the nuclear envelope of nuclear lncRNAs. This study documents the development of a nucleus-specific RNA interference (RNAi) nanoparticle (NP) platform for the targeted regulation of the nuclear lncRNA function, in order to effectuate successful cancer therapy. An NTPA (nucleus-targeting peptide amphiphile) and an endosomal pH-responsive polymer make up the novel RNAi nanoplatform in development, which is capable of complexing siRNA. The nanoplatform is capable of accumulating greatly in the tumor tissues and being internalized by tumor cells, following intravenous administration. The exposed complexes of the NTPA/siRNA may conveniently escape from the endosome with the pH-triggered NP disassociation, following which it can target the nucleus by specifically interacting with the importin α/β heterodimer. In orthotopic and subcutaneous xenograft tumor models, this would result in a notable suppression of the expression of nuclear lncNEAT2 as well as greatly impede the growth of tumors in liver cancer.

PH-sensitive packaging of cationic particles by an anionic block copolymer shell

Cationic non-viral vectors show great potential to introduce genetic material into cells, due to their ability to transport large amounts of genetic material and their high synthetic versatility. However, designing materials that are effective without showing toxic effects or undergoing non-specific interactions when applied systemically remains a challenge. The introduction of shielding polymers such as polyethylene glycol (PEG) can enhance biocompatibility and circulation time, however, often impairs transfection efficiency. Herein, a multicomponent polymer system is introduced, based on cationic and hydrophobic particles (P(nBMA46-co-MMA47-co-DMAEMA90), (PBMD)) with high delivery performance and a pH-responsive block copolymer (poly((N-acryloylmorpholine)-b-(2-(carboxy)ethyl acrylamide)) (P(NAM72-b-CEAm74), PNC)) as shielding system, with PNAM as alternative to PEG. The pH-sensitive polymer design promotes biocompatibility and excellent stability at extracellular conditions (pH 7.4) and also allows endosomal escape and thus high transfection efficiency under acidic conditions. PNC shielded particles are below 200 nm in diameter and showed stable pDNA complexation. Further, interaction with human erythrocytes at extracellular conditions (pH 7.4) was prevented, while acidic conditions (pH 6) enabled membrane leakage. The particles demonstrate transfection in adherent (HEK293T) as well as difficult-to-transfect suspension cells (K-562), with comparable or superior efficiency compared to commercial linear poly(ethylenimine) (LPEI). Besides, the toxicity of PNC-shielded particles was significantly minimized, in particular in K-562 cells and erythrocytes. In addition, a pilot in vivo experiment on bone marrow blood cells of mice that were injected with PNC-shielded particles, revealed slightly enhanced cell transfection in comparison to naked pDNA. This study demonstrates the applicability of cationic hydrophobic polymers for transfection of adherent and suspension cells in culture as well as in vivo by co-formulation with pH-responsive shielding polymers, without substantially compromising transfection performance.Graphical

Research on preparation and properties of pH responsive superhydrophobic coating modified by SEBS

Smart materials with reversible wettability have attracted a lot of attention for application in sewage treatment. In this work, a pH-responsive polymer was prepared via the one-step free radical polymerization of 3-(trimethoxysilyl) acrylate and 2-dimethylaminoethyl methacrylate. The obtained pH-responsive polymer was then coated with a hydrogenated styrene–ethylene–butadiene–styrene block copolymer to endow the material with pH-responsive switchable superhydrophilic and superhydrophobic properties. Due to the excellent self-cleaning and mechanical stability of the coating, it was used to modify paper, which was then successfully utilized in the treatment of oily wastewater, showing great potential for use in advanced applications.

Preparation, Characterization and In Vitro Evaluation of Eudragit S100-Coated Bile Salt-Containing Liposomes for Oral Colonic Delivery of Budesonide.

The aim of this study was to prepare a liposomal formulation of a model drug (budesonide) for colonic delivery by incorporating a bile salt (sodium glycocholate, SGC) into liposomes followed by coating with a pH-responsive polymer (Eudragit S100, ES100). The role of the SGC is to protect the liposome from the emulsifying effect of physiological bile salts, while that of ES100 is to protect the liposomes from regions of high acidity and enzymatic activity in the stomach and small intestine. Vesicles containing SGC were prepared by two preparation methods (sonication and extrusion), and then coated by ES100 (ES100-SGC-Lip). ES100-SGC-Lip showed a high entrapment efficiency (>90%) and a narrow size distribution (particle size = 275 nm, polydispersity index < 0.130). The characteristics of liposomes were highly influenced by the concentration of incorporated SGC. The lipid/polymer weight ratio, liposome charge, liposome addition, and mixing rate were critical factors for efficient and uniform coating. In vitro drug release studies in various simulated fluids indicate a pH-dependent dissolution of the coating layer, and the disintegration process of ES100-SGC-Lip was evaluated. In conclusion, the bile salt-containing ES100-coated liposomal formulation has potential for effective oral colonic drug delivery.

Turning Hot into Cold: Immune Microenvironment Reshaping for Atherosclerosis Attenuation Based on pH-Responsive shSiglec-1 Delivery System.

Current atherosclerosis treatment is based on a combination of cholesterol-lowering medication and low-fat diets; however, the clinical effect is unsatisfactory. It has been shown that the level of immune cell infiltration and pro-inflammatory factors in the atherosclerotic immune microenvironment (AIM) play important roles in the development and progression of atherosclerosis. Therefore, we hypothesized that reshaping "hot AIM" into "cold AIM" could attenuate atherosclerosis. For this purpose, we designed a pH-responsive and charge-reversible nanosystem, referred to as Au-PEI/shSiglec-1/PEI-acetylsalicylic acid (ASPA NPs) to effectively deliver shSiglec-1, which blocked the interactions between macrophages with CD8+ T/NKT cells, thus inhibiting immune cell infiltration. Further, we demonstrated that acetylsalicylic acid (ASA), detached from the pH-responsive PEI-ASA polymer, and inhibited lipid accumulation in macrophage, thereby decreasing the lipid antigen presentation. Additionally, reduced macrophage-produced inflammatory factors by ASA and low CD8+ T/NKT cell infiltration levels synergistically inhibit Th17 cell differentiation, thus further dramatically attenuating inflammation in AIM by decreasing the IL-17A production. Eventually, ASPA NPs efficiently reshaped AIM by inhibiting immune cell infiltration, lipid antigen presentation, and pro-inflammation, which provided a feasible therapeutic strategy for atherosclerosis immunotherapy.

Development of a pH-Responsive Polymer Based on Hyaluronic Acid Conjugated with Imidazole and Dodecylamine for Nanomedicine Delivery

Development of a pH-Responsive Polymer Based on Hyaluronic Acid Conjugated with Imidazole and Dodecylamine for Nanomedicine Delivery

Self-oscillating polymer membranes with chemically fueled pore size oscillation mediated by pH-responsive polymer

Soft-matter materials research has considerably evolved in the last decades, mainly by promoting responsive polymer systems. Up to now, the dynamic behavior in materials was always reached by the action of an outside trigger (pH, light, etc..). This constraint has been relieved in a new class of materials that experienced self-oscillation. In this work, the self-regulating pH cycles caused by a chemical oscillator will induce autonomous pH-sensible polymer chain movements at the membrane interface, causing continuous pore-size oscillation cycles and thus a self-oscillating flux. This work involved the functionalisation of polyethersulfone commercial membranes to achieve pore size oscillations. The pH-sensitive polymer, poly(methacrylic acid) (PMAA), was obtained by deprotection of poly(tert-butyl methacrylate) (PtBuMA) synthesized by RAFT polymerization. To adapt this functionalisation to all types of commercial membranes, a thin layer of polydopamine (PDA) was deposited on the top of the membrane, which then allows a Michael-thiol-ene reaction between PDA and thiol-functionalized PMAA, obtained from prior aminolysis of PtBuMA. The functionalisation steps were characterized by XPS, SEM, water contact angle, and permeability measurements. Membranes were then placed in a filtration system containing a chemical pH oscillator to control the PMAA chain conformation through the pH cycle. Water permeation analysis showed a dependence between permeability and PMAA conformation, leading to the conclusion that there is indeed a continuous oscillation in membrane pore size.

Single Artificial Ion Channels with Tunable Ion Transport Based on the Surface Modification of pH-Responsive Polymers.

Artificial ion channels with tunable ionic transport control and intelligent iontronic functions at the nanoscale have a wide application in logic computing and biosensing. Although some artificial ion channels with smart ion transport characteristics have been developed, most of them are constructed on porous membranes with undefined channel numbers. It is still challenging to achieve multiple ion transport features in single nanochannels and to control the ion flow more accurately with excellent repeatability. In this paper, a design strategy is presented to fabricate pH-responsive ion channels with various ion transport features based on a single polydimethylsiloxane (PDMS) nanochannel. The single-ion nanochannel developed by this approach can be further integrated into electronic systems on a chip. Three types of artificial ion channels are demonstrated and investigated systematically in this work. With symmetric or asymmetric pH stimuli, these ion channels can alternatively change their working states among an opened state, a closed state, and an ionic diode state. Four different ion transport features can be realized in a triple-gated ion channel system. With these advantages of the design, it is promising to build smart nanofluidic iontronic devices with widespread applicability in energy conversions, active ion transport control, and biological analysis.

Nonequilibrium regulation of interfacial chemistry for transient macroscopic supramolecular assembly

HypothesisMacroscopic nonequilibrium assembly helps to interpret the interfacial assembly mechanism and promotes the creation of self-adaptive chemical systems for potential applications such as controlled release and mass transfer. We propose that the precise macroscopic nonequilibrium assembly can be achieved by rationally integrating pH-responsive hybrid polymer hydrogels with the urea-urease clock reaction. ExperimentsHerein, pH-responsive and urease-containing polyelectrolyte hydrogels were fabricated for achieving macroscopic nonequilibrium assembly. Optical microscopy was used to visualize the interface of the macroscopic assemblies. Tensile tests were performed to investigate the adhesion strength of the assemblies and the modulus of the hydrogels. The charges and electric field distribution at the hydrogel surface were estimated by zeta potential measurements. Furthermore, an in situ sewing-growing method for fabricating hybrid polymer hydrogels with modularized surface chemistry was presented to achieve precise nonequilibrium assembly. FindingsThe realization of precise macroscopic nonequilibrium assembly relies on the transient electrostatic attraction between the hybrid polymer hydrogels, which lays the foundation for yielding transient macroscopic supramolecular devices potentially useful for timed release. The stability and lifetime of the transient assemblies can be controlled by adjusting the hydrogel synthesis parameters and fuel compositions, and the macroscopic nonequilibrium assembly can be repeated by refueling the system.

Heat-stable liposomes from milk fat globule membrane phospholipids for pH-triggered delivery of hydrophilic and lipophilic bioactives

Heat-stable, multivitamin-loaded, and surface-coated liposomes tailored for pH-triggered delivery of both lipophilic and hydrophilic bioactives were synthesized from a cocktail of milk fat globule membrane (MFGM) phospholipids, supercritically extracted from buttermilk powder. Liposomes from MFGM-phospholipids (ML) were fabricated using a novel organic solvent free process based on venturi-based rapid expansion of a supercritical solution. A commercially available pH-responsive polymer, Eudragit® S100 was used to coat ML (Eu-ML). Eu-MLs were heated to 60, 75, and 90 °C for 30 min and were observed to be heat-stable as established by CLSM images, structural characterizations, and encapsulation efficiency measurements. Coating of liposomes with Eudragit® S100 protected encapsulated payload from deleterious gastric environment and facilitated site-specific pH-triggered release in the simulated intestinal condition. This study established a green method to fabricate heat-stable liposomal vehicles for pH-triggered delivery of bioactive compounds with excellent potential for scale-up and applications in the food, pharmaceutical, and cosmetic industries.

Green Synthesis of De Novo Bioinspired Porous Iron-Tannate Microstructures with Amphoteric Surface Properties

Bioinspired porous microstructures of iron-tannate (Fe(III)-TA) coordination polymer framework were synthesized by catenating natural tannic acid with iron(II), using a scalable aqueous synthesis method in ambient conditions. The chemical composition, morphology, physiochemical properties, and colloidal stability of microstructures were elucidated. The surface area (SBET) and the desorption pore volume were measured to be 70.47 m2/g and 0. 44 cm3/g, respectively, and the porous structure was confirmed with an average pore dimension of ~27 nm. Microstructures were thermally stable up to 180 °C, with an initial weight loss of 13.7% at 180 °C. They exhibited high chemical stability with pH-responsive amphoteric properties in aqueous media at pH levels ranging from 2 to 12. Supporting their amphoteric sorption, microstructures exhibited rapid removal of Pb+2 from water, with 99% removal efficiency, yielding a maximum sorption capacity of 166.66 mg/g. Amphoteric microstructures of bioinspired metal–phenolate coordination polymers remain largely unexplored. Additionally, natural polyphenols have seldomly been used as polytopic linkers to construct both porous and pH-responsive amphoteric coordination polymer frameworks with a robust structure in both acidic and basic media. Thus, this de novo porous microstructure of Fe(III)-TA and its physiochemical surface properties have opened new avenues to design thermally and chemically stable, eco-friendly, low-cost amphoteric sorbents with multifunctionality for adsorption, ion exchange, separation, storage, and sensing of both anions and cations present in heterogeneous media.

Synthesis of Chemically Cross-Linked pH-Sensitive Hydrogels for the Sustained Delivery of Ezetimibe.

In recent years, pH-sensitive hydrogels have been developed for the delivery of therapeutic agents to specific target sites that have a defined pH range. The use of pH-responsive polymers in hydrogels allows drug delivery to the desired pH range of the target organ. The primary aim is to increase the retention time of the drug in the small intestine by utilizing the swelling mechanism of the hydrogel at intestinal pH. In this study, polyethylene glycol (PEG) was used as a polymer to formulate a pH-sensitive hydrogel of Ezetimibe to deliver the drug to the small intestine where it inhibits the absorption of cholesterol. Design Expert software was applied to design and optimize the trial formulations in order to obtain an optimized formulation that has all the desired characteristics of the hydrogels. The PEG/Acrylic Acid hydrogels showed the maximum swelling at pH 6.8, which is consistent with the pH of the small intestine (pH 6–7.4). The maximum entrapment efficiency of the hydrogels was 99%. The hydrogel released 80–90% of the drug within 24 h and followed first-order release kinetics, which showed that the release from the drug was sustained. Hence, the results showed that the choice of a suitable polymer can lead to the development of an efficient drug-loaded hydrogel that can deliver the drug at the specific pH of the target organ.

PH-Responsive Polymer Nanoparticles for Efficient Delivery of Cas9 Ribonucleoprotein With or Without Donor DNA.

Clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) may offer new therapeutics for genetic diseases through gene disruption via nonhomologous end joining (NHEJ) or gene correction via homology-directed repair (HDR). However, clinical translation of CRISPR technology is limited by the lack of safe and efficient delivery systems. Here, facilely fabricated pH-responsive polymer nanoparticles capable of safely and efficiently delivering Cas9 ribonucleoprotein alone (termed NHEJ-NP, diameter = 29.4nm), or together with donor DNA (termed HDR-NP, diameter = 33.3nm) are reported. Moreover, intravenously, intratracheally, and intramuscularly injected NHEJ-NP induces efficient gene editing in mouse liver, lung, and skeletal muscle, respectively. Intramuscularly injected HDR-NP also leads to muscle strength recovery in a Duchenne muscular dystrophy mouse model. NHEJ-NP and HDR-NP possess many desirable properties including high payload loading content, small and uniform sizes, high editing efficiency, good biocompatibility, low immunogenicity, and ease of production, storage, and transport, making them great interest for various genome editing applications with clinical potentials.

PH-responsive and CD44-targeting polymer micelles based on CD44p-conjugated amphiphilic block copolymer PEG-b-HES-b-PLA for delivery of emodin to breast cancer cells

Herein, an amphiphilic block copolymer CD44-targeting peptide-conjugated polyethylene glycol-block-hydroxyethyl starch-block-poly (L-lactic acid) (CD44p-conjugated PEG-b-HES-b-PLA) are synthesized, which could self-assemble into the pH-responsive and CD44-targeting polymer micelles against breast cancer cells MDA-MB-231. Emodin (Emo) is a natural anthraquino with pharmacological activities in anti-tumor effects. However, Emo suffers from poor water solubility, low biocompatibility, rapid systemic elimination, and off-target side effects, resulting in unsatisfactory treatment outcomes. Nanotechnology-based drug delivery systems have proven great potential for cancer chemotherapy. The constructed polymeric micelles Emo@CD44p-PM have exhibited an average size of 154.5 ± 0.9 nm characterized by DLS and TEM. Further, the Emo@CD44p-PM have effective Emo-loading capacity, good thermal stability, and pH responsiveness. Intracellular uptake study shows the enhanced cellular internalization of Emo@CD44p-PM due to the increased exposure of CD44p enhances the cellular internalization of Emo@CD44p-PM effectively. Furthermore, the in vitro results showed Emo@CD44p-PM has been observed good biocompatibility and anti-tumor effects. Therefore, the polymeric micelles Emo@CD44p-PM provide a promising delivery strategy of targeted therapy for breast cancer.

PH Responsive Polyurethane for the Advancement of Biomedical and Drug Delivery.

Due to the specific physiological pH throughout the human body, pH-responsive polymers have been considered for aiding drug delivery systems. Depending on the surrounding pH conditions, the polymers can undergo swelling or contraction behaviors, and a degradation mechanism can release incorporated substances. Additionally, polyurethane, a highly versatile polymer, has been reported for its biocompatibility properties, in which it demonstrates good biological response and sustainability in biomedical applications. In this review, we focus on summarizing the applications of pH-responsive polyurethane in the biomedical and drug delivery fields in recent years. In recent studies, there have been great developments in pH-responsive polyurethanes used as controlled drug delivery systems for oral administration, intravaginal administration, and targeted drug delivery systems for chemotherapy treatment. Other applications such as surface biomaterials, sensors, and optical imaging probes are also discussed in this review.

Preparation of colloidal nanoparticles PVA-PHEMA from hydrolysis of copolymers of PVAc-PHEMA as anticancer drug carriers

The novel pH-responsive polymer nanoparticles have been widely used for drug delivery and cancer therapy. The pH-sensitive nanoparticles include chemical structures that can accept or donate protons in response to an environmental pH change. Polybases which mostly contain alkaline groups such as amines and hydroxy, accept protons at low pH and are neutral at higher pH values. This study aimed to prepare pH-sensitive colloidal amphiphilic poly(vinyl alcohol-2-hydroxyethyl methacrylate) (PVA-PHEMA) copolymers in cancer therapy applications. For this purpose, poly(vinyl acetate-2-hydroxyethyl methacrylate) (PVAc-PHEMA) copolymer nanoparticles were synthesized in different polymerization medium fractions from water and methanol and different monomer feed concentration. Then acetate groups were hydrolyzed, and the PHEMA-PVA nanoparticles were synthesized. The nanoparticles were further characterized using dynamic light scattering, Fourier transform infrared spectroscopy, scanning electron microscopy, and thermogravimetric analysis to identify the structural and morphological changes. The Methotrexate (MTX) was loaded into the nanoparticles, and drug release kinetics were evaluated. The results confirmed that PHEMA-PVA copolymeric nanoparticles could be favorably used in cancer therapy.

Smart Nanocarrier Based on Poly(oligo(ethylene glycol) methyl ether acrylate) Terminated pH-Responsive Polymer Brushes Grafted Mesoporous Silica Nanoparticles

A platform technology based on inorganic/organic nanoparticles for carrying drugs could be of enormous potential benefit in treating cancer. Surface modification of the nanoparticles with pH-responsive and biocompatible polymers can improve the selectivity and targeting toward the tumor cells. Polyethylene glycol (PEG) and its derivatives being present on the surface could enhance the ability to tailor nanomaterial hydrophilicity and to resist the adhesion of proteins and/or cells. Herein, we report a new nanoplatform based on mesoporous silica nanoparticles (MSNs) conjugated with poly(2-(diethylamino) ethyl methacrylate) (PDEAEMA) brushes as a candidate for stimuli-responsive intracellular drug delivery system. Alkyl bromide functional initiators (end-functionalized PDEAEMA brushes) were derivatized to amine, followed by the reaction with ethylene sulfide and poly(oligo(ethylene glycol) methyl ether acrylate (POEGMEA). Using X-ray photoelectron spectroscopy (XPS) to examine the attachment of POEGMEA, it was found that the POEGMEA molecules in the outer surface of PDEAEMA brushes have been successfully reacted with thiol groups, as indicated by the increase in the peak intensity of the C–O group at 286.5 eV. Brush-modified silica hybrids have an average diameter of ca. 250 nm, as estimated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Rhodamine B dye was loaded into the brush-modified silica hybrids nanoparticles with loading capacity of ca. 74%. The accumulated dye released from brush-modified particles in acidic media was approximately 60%, whereas the dye amount release in basic media was less than 15% after 10 h exposure time. Alamar Blue assay was used to assess the cytotoxicity of MSNs–PDEAEMA, MSNs–PDEAEMA–SH, and MSNs–PDEAEMA–POEGMEA. The results show that all three nanosystems were non-toxic to hMSC with an increase in cell proliferation for MSNs–PDEAEMA–POEGMEA at 50 µg/mL after both 24 and 48 h of incubation.

PH-Responsive Polymer Nanomaterials for Tumor Therapy.

The complexity of the tumor microenvironment presents significant challenges to cancer therapy, while providing opportunities for targeted drug delivery. Using characteristic signals of the tumor microenvironment, various stimuli-responsive drug delivery systems can be constructed for targeted drug delivery to tumor sites. Among these, the pH is frequently utilized, owing to the pH of the tumor microenvironment being lower than that of blood and healthy tissues. pH-responsive polymer carriers can improve the efficiency of drug delivery in vivo, allow targeted drug delivery, and reduce adverse drug reactions, enabling multifunctional and personalized treatment. pH-responsive polymers have gained increasing interest due to their advantageous properties and potential for applicability in tumor therapy. In this review, recent advances in, and common applications of, pH-responsive polymer nanomaterials for drug delivery in cancer therapy are summarized, with a focus on the different types of pH-responsive polymers. Moreover, the challenges and future applications in this field are prospected.