Polymer-drug and polymer-protein conjugated nanocarriers: Design, drug delivery, imaging, therapy, and clinical applications.

Polymer-drug conjugates and polymer-protein conjugates have been pivotal in the realm of drug delivery systems for over half a century. These polymeric drugs are characterized by the conjugation of therapeutic molecules or functional moieties to polymers, enabling a range of benefits including extended circulation times, targeted delivery, controlled release, and decreased immunogenicity. This review delves into recent advancements and challenges in the clinical translations and preclinical studies of polymer-drug conjugates and polymer-protein conjugates.

Lycopene Promotes Osteogenesis and Reduces Adipogenesis through Regulating FoxO1/PPARγ Signaling in Ovariectomized Rats and Bone Marrow Mesenchymal Stem Cells.

Recent interest in preventing the development of osteoporosis has focused on the regulation of redox homeostasis. However, the action of lycopene (LYC), a strong natural antioxidant compound, on osteoporotic bone loss remains largely unknown. Here, we show that oral administration of LYC to OVX rats for 12 weeks reduced body weight gain, improved lipid metabolism, and preserved bone quality.

pH-responsive polyzwitterion covered nanocarriers for DNA delivery.

The success of gene therapy relies on gene nanocarriers to achieve therapeutic effects in vivo. Surface shielding of poly(ethylene glycol) (PEG), known as PEGylation, onto gene delivery carriers is a predominant strategy for extending blood circulation and improving therapeutic outcomes in vivo. Nevertheless, PEGylation frequently compromises the transfection efficiency by decreasing the interactions with the cellular membrane of the targeted cells, thereby preventing the cellular uptake and the subsequent endosomal escape.

Polymeric ligands comprising sulfur-containing amino acids for targeting tumor-associated amino acid transporters.

Various cancer cells overexpress L-type amino acid transporter 1 (LAT1) to take up a large number of neutral amino acids such as phenylalanine and methionine, and LAT1 transporter should be a promising target for cancer diagnosis and therapy. However, only a few studies reported drug delivery systems targeting LAT1 probably due to limited knowledge about the interaction between LAT1 and its substrate. Here, we developed polymers having methionine (Met)- or cysteine (Cys)-like structures on their side chains to examine their affinity with LAT1.

Green credit policy and the liquidity risks of heavily polluting enterprises.

As a kind of enterprises most affected by green policies-heavily polluting enterprises, whether the government's relevant policies can achieve its policy goals and what impact will be exerted on such enterprises is a critical issue. Based on the data of listed heavily polluting enterprises in China from 2007 to 2020, this paper uses the difference in differences model to test the impact of green credit policies on the liquidity risk of heavily polluting enterprises. The results show that the green credit policies intensify the liquidity risk of heavily polluting enterprises.

Cancerous pH-responsive polycarboxybetaine-coated lipid nanoparticle for smart delivery of siRNA against subcutaneous tumor model in mice.

Lipid nanoparticles (LNPs) have been commonly used as a vehicle for nucleic acids, such as small interfering RNA (siRNA); the surface modification of LNPs is one of the determinants of their delivery efficiency especially in systemic administration. However, the applications of siRNA-encapsulated LNPs are limited due to a lack effective systems to deliver to solid tumors. Here, we report a smart surface modification using a charge-switchable ethylenediamine-based polycarboxybetaine for enhancing tumor accumulation via interaction with anionic tumorous tissue constituents due to selective switching to cationic charge in response to cancerous acidic pH.

Systemically Applicable Glutamine-Functionalized Polymer Exerting Multivalent Interaction with Tumors Overexpressing ASCT2.

Transporter ASCT2, which predominantly imports glutamine (Gln), is overexpressed in a variety of cancer cells, and targeting ASCT2 is expected to be a promising approach for tumor diagnosis and therapy. In this work, we designed a series of glutamine-modified poly(l-lysine) (PLys(Gln)) homopolymers and PEG-PLys(Gln) block copolymers and investigated their tumor-targeting abilities. With increasing degree of polymerization in the PLys(Gln) homopolymers, their cellular uptake was gradually enhanced through multivalent interactions with ASCT2.

Polymeric Iron Chelators Enhancing Pro-Oxidant Antitumor Efficacy of Vitamin C by Inhibiting the Extracellular Fenton Reaction.

Intravenously injected high-dose vitamin C (VC) induces extracellular HO, which can penetrate into the tumor cells and suppress tumor growth. However, extracellular labile iron ions in the tumor decompose HO via the Fenton reaction, limiting the therapeutic effect. In this regard, we recently developed a polymeric iron chelator that can inactivate the intratumoral labile iron ions.

Potential urinary monitoring of the enhanced permeability and retention effect using MMP-2-responsive poly(ethylene glycol) derivatives.

The enhanced permeability and retention (EPR) effect is fundamental to tumor-targeted drug delivery using nanoparticles. However, recent studies reported heterogeneity of the EPR effect, and companion diagnostics are considered to be key to predicting and optimizing the benefits of the EPR effect. Here, as a new material to simply endow the function of companion diagnostics to nanoparticles, we designed a poly(ethylene glycol) (PEG) derivative conjugated with low molecular fluorescent dye through synthetic substrate linker that can be cleaved in response to MMP-2, which is overexpressed in tumor extracellular matrix.

Vitrimerization: Converting Thermoset Polymers into Vitrimers.

Thermoset polymers with permanently cross-linked networks have outstanding mechanical properties and solvent resistance, but they cannot be reprocessed or recycled. On the other hand, vitrimers with covalent adaptable networks can be recycled. Here we provide a simple and practical method coined as "vitrimerization" to convert the permanent cross-linked thermosets into vitrimer polymers without depolymerization.

Changes and Diurnal Variation of Visual Quality after Orthokeratology in Myopic Children.

Purpose: To assess the changes and the diurnal variation of visual quality after orthokeratology in myopic children.

Methods: Forty-four eyes of 22 subjects with a mean age of 10.55 ± 1.

Covalent self-assembled nanoparticles with pH-dependent enhanced tumor retention and drug release for improving tumor therapeutic efficiency.

Developing a smart drug delivery system with enhanced tumor retention at the tumor site, and rapid intracellular drug release promises to improve the therapeutic index and mitigate side effects. To this end, covalent phenylboronic acid (PBA)-based self-assembly nanoparticles (BNPs) consisting of pH-responsive cores and detachable poloxamer 188 shells were constructed for loading doxorubicin (DOX) in a simple process. The poloxamer 188 coating could be easily detached when the breakage of the borate ester bonds in the external nanocores was initially triggered in the tumor extracellular weak acid environment.

Multifunctional nanoplatform for enhanced photodynamic cancer therapy and magnetic resonance imaging.

Co-delivery of photosensitizers and synergistic agents by one single nanoplatform is interesting for enhancing photodynamic therapy (PDT) of cancer. Here, a multifunctional nanoplatform for enhanced photodynamic therapy and magnetic resonance imaging of cancer was constructed. The poly (lactide-co-glycolide) (PLGA) nanoparticles (NPs) loaded with hematoporphyrin monomethyl ether (HMME) were coated with multifunctional manganese dioxide (MnO) shells, which were designed as PLGA/HMME@MnO NPs.