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A mass spectrometric platform was built for in-depth profiling of mutational landscape of cis-diol metabolites from the healthy to primary liver cancer (PLC) patients. This method enabled more precise PLC diagnosis than protein marker-based methods.

Accurately analysing the particular glycosylation status of protein biomarkers is of significant importance in the precise, early diagnosis of cancer. Existing methods mainly rely on the use of antibodies and lectins. However, due to the macroscopic and microscopic heterogeneity of glycans, precise analysis of glycosylation status still remains a challenge. Molecularly imprinted polymers (MIPs), as a synthetic alternative to antibodies or lectins, may provide new solutions but have not yet been explored. Herein, we report an appealing strategy called triple MIP-based plasmonic immunosandwich assay (triMIP-PISA) for precise cancer diagnosis in terms of the relative glycosylation expression of glycoprotein biomarkers. As proof of the principle, alpha fetoprotein (AFP), which has been used as a clinical biomarker for early detection of hepatocellular carcinoma (HCC), as well as its

Exploring new targets and developing novel targeted therapies are urgently needed for neuroblastoma therapy. Polysialic acid (polySia), a linear homopolymer of sialic acid units that correlates well with tumor progression and poor prognosis, has emerged as a potential target for neuroblastoma. However, the lack of polySia-specific binding reagents has severely limited the development of polySia-targeting therapeutics for neuroblastoma. Herein, the construction of polySia-targeting nanomissiles via molecular imprinting for the photothermal therapy of neuroblastoma is reported. Oligosialic acid (oligoSia) containing 3-4 units is considered as a characteristic structure for the recognition of polySia, while oligoSia containing 4-7 units digested from polySia is employed as the template. Via boronate-affinity controllable oriented surface imprinting, oligoSia-imprinted nanoparticles (oSia-MIP) are prepared. The oSia-MIP allows for specifically recognizing polySia and targeting polySia overexpressed neuroblastoma cells in vitro and in vivo. oSia-MIP loaded with indocyanine green is prepared and experimentally demonstrated to be a potent targeted photothermal therapeutic for neuroblastoma. Equipping the core substrate with functional entities, the developed polySia targeting nanoplatform can be accommodated to various therapeutic modalities, holding great promise for neuroblastoma targeted therapy.

Blocking the PD-1/PD-L1 immune checkpoint has emerged as a promising strategy in cancer immunotherapy, in which monoclonal antibodies are predominately used as inhibitors. Despite their remarkable success, monoclonal antibody-based therapeutics suffer from drawbacks due to the use of antibodies, such as high cost, low stability and high frequency of immune-related adverse effects. Therefore, novel anti-PD-1/PD-L1 therapeutics that can address these issues are of significant importance. Herein, we report a molecularly imprinted polymer (MIP) based PD-1 nano inhibitor for blocking the PD-1/PD-L1 axis. The anti-PD-1 nanoMIP was rationally designed and engineered by epitope imprinting using the N-terminal epitope of PD-1 as the binding site. The anti-PD-1 nanoMIP showed good specificity and high affinity towards PD-1, yielding a disassociation constant at the 10

Prodrug and drug delivery systems are two effective strategies for improving the selectivity of chemotherapeutics. Molecularly imprinted polymers (MIPs) have emerged as promising carriers in targeted drug delivery for cancer treatment, but they have not yet been integrated with the prodrug strategy. Reported here is an MIP‐based smart prodrug delivery system for specific targeting, prolonged retention time, and tumor microenvironment‐triggered release. 5′‐Deoxy‐5‐fluorocytidine (DFCR) and sialic acid (SA) were used as a prodrug and a marker for tumor targeting, respectively. Their co‐imprinted nanoparticles were prepared as a smart carrier. Prodrug‐loaded MIP specifically and sustainably accumulated at the tumor site and then gradually released. Unlike conventional prodrug designs, which often require in‐liver bioconversion, this MIP‐based prodrug delivery is liver‐independent but tumor‐dependent. Thus, this study opens new access to the development of smart prodrug delivery nanoplatforms., A molecularly imprinted polymer (MIP) based smart prodrug delivery nanoplatform was demonstrated with the ability to specifically target tumor sites with prolonged retention time and gradual tumor microenvironmental pH‐triggered release. The MIP‐based prodrug delivery is liver‐independent but tumor‐dependent, which not only greatly enhances tumor specificity but also expands the scope of applicable prodrugs.

Molecularly imprinted polymers (MIPs) are chemically synthesized affinity materials with tailor‐made binding cavities complementary to the template molecules in shape, size, and functionality. Recently, engineering MIP‐based nanomedicines to improve cancer therapy has become a rapidly growing field and future research direction. Because of the unique properties and functions of MIPs, MIP‐based nanoparticles (nanoMIPs) are not only alternatives to current nanomaterials for cancer therapy, but also hold the potential to fill gaps associated with biological ligand‐based nanomedicines, such as immunogenicity, stability, applicability, and economic viability. Here, we survey recent advances in the design and fabrication of nanoMIPs for cancer therapy and highlight their distinct features. In addition, how to use these features to achieve desired performance, including extended circulation, active targeting, controlled drug release and anti‐tumor efficacy, is discussed and summarized. We expect that this minireview will inspire more advanced studies in MIP‐based nanomedicines for cancer therapy., This minireview surveys recent advances in research on molecularly imprinted polymer nanoparticles (nanoMIPs) for cancer therapy and highlights the distinct features of nanoMIPs for the rational design and construction of cancer nanomedicines with desired performances, including extended circulation, active targeting, controlled drug release, and antitumor efficacy.

Resin-impregnated paper (RIP) bushing has gained significant interest due to its extended application in Extra High Voltage (EHV) and Ultra High Voltage (UHV) electricity transmission systems. However, the design criterion of its overall structure, the geometry parameters of the condenser layers, and stress release devices, etc., are still not fully understood. This article proposes a unique electric field optimization technique to integrate both the analytical and the numerical methods. The charge simulation method (CSM) is employed to create the overall equipotential surface, within which the finite element analysis (FEA) is adapted to study the localized field enhancement effects, taking into consideration the multi-physics coupled fields. A case study is performed on an actual UHV bushing. The results are compared to the traditional methods, to demonstrate the benefit of the hybrid method.

The glycosylation pattern of alpha fetoprotein (AFP) paves the basis for precise early diagnosis of hepatocellular carcinoma (HCC). However, existing analytical methods ignore the contribution of terminal sialic acid, which has been reported to be highly connected with HCC. Besides, the development of diagnostic assays is severely hindered by the preparation of anti-glycans antibodies. Molecularly imprinted polymers (MIPs), as synthetic antibody mimics, provide unique strengths to address these issues. Herein, we report a MIPs-based dual-modal ratiometric immunoassay for precise HCC diagnosis. Using a "pit one against ten" MIP to recognize a subset of glycans containing sialic acid and/or core fucose, we demonstrated our assay exhibited improved precision as compared with ELISA. This assay provided not only a glycoform-resolved method for precise HCC diagnosis, but also a new paradigm for developing antibody mimics via molecular imprinting towards challenging biomedical applications.

Combination delivery systems composed of injectable hydrogels and drug-incorporated micelles or nanoparticles with tunable and convenient properties for clinical operation and storage are urgently demanded in regional cancer chemotherapy to prolong and control drug release, enhance antitumor efficiency and decrease side effects. Previously, we developed a novel thermosensitive amphiphilic triblock copolymer, poly(e-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)–poly(ethylene glycol)–poly(e-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT), and fabricated a reconstituted “two into one” combination system of thermosensitive injectable hydrogel PTX/PECTGel, assembled from paclitaxel (PTX)-loaded PECT nanoparticles (NPs). PTX/PECTGel could be stored as freeze-dried powders of paclitaxel-loaded PECT NPs, which could be reconstituted into aqueous fluid dispersions at ambient temperature just by mixing with water after gentle stirring for several minutes, and form a hydrogel at the injected site in vivo. Herein, the drug release, in vivo morphology, antitumor efficiency and pharmacokinetic properties of PTX/PECTGel were evaluated. The PTX/PECTGel combination system could continuously release PTX in a near linear manner over 42 days in vitro, and simultaneously, PTX/PECT NPs containing 75% of the total released PTX could dissociate from the PTX/PECTGel. PTX/PECTGel exhibited remarkable in vitro anti-proliferative activities against Ehrlich ascites carcinoma (EAC) cancer cells. The peritumorally or intratumorally injected PECT gel could cover the entire surface or fill up the interior space of the tumor, respectively. A single peritumoral injection of the PTX/PECTGel formulation at a low dosage of 10 mg kg−1 could completely inhibit the growth of an EAC tumor inoculated in Balb/c mice after the first week, and the inhibition could be sustained for more than 21 days. The plasma pharmacokinetic study demonstrated that PTX/PECTGel could greatly decrease the systemic exposure of PTX, as confirmed by the rather low plasma concentration. On the other hand, the PTX concentration in normal tissues with the intratumoral injection of PTX/PECTGel was approximately 2 μg g−1, which was 3–10 times lower than that with the intraperitoneal or intratumoral injection of Taxol®, implying fewer off-target side effects. These data confirmed that the PTX/PECTGel combination local delivery system could vastly prolong the in vitro and in vivo paclitaxel release, enhance the local tumor inhibition effect and lower the systemic exposure and tissue distribution of paclitaxel. Hence, the “two into one” PTX/PECTGel system holds underlying value for regional cancer chemotherapy.

Combining functions of multidrug co-delivery and multistep release in biocompatible membranes is an oncoming requirement for improving therapeutic process. In this paper, a kind of polymer micelle-embedded core/shell nanofibrous membranes was prepared by a simple and effective technology of coaxial electrospinning. The nanofibers were composed of hydrophobic polycaprolactone (PCL) shell layer and hydrophilic polyvinyl pyrrolidone (PVP) core in which more than 40 % (w/w) amphiphilic block copolymer mPECT micelles (mPECT Ms) were embedded. Two bioactive drugs, lincomycin hydrochloride (LH) as the anti-inflammatory drug and Vitamin E (VE) as the fibrinolysis drug, were effectively loaded in the PVP core of the fibers and mPECT Ms, respectively. The SEM and TEM figures showed the smooth core/shell nanofibers with interiorly even-distributed micelles were fabricated. The XRD patterns illustrated that drugs distributed amorphously in the composite mats without crystallization. The in vitro degradation test also gave evidence to the time consistency between the degradation time of this material and potential occurrence time of adhesion. Furthermore, the in vitro release profiles indicated that both drugs were controlled to release sustainably for more than 15 days, and multistep release pattern of the early fast release of LH companied by the slow VE release was achieved. Therefore, the polymer micelle-embedded core/shell nanofibrous membranes could provide a new strategy for therapeutic application to realize multidrug co-delivery and multistep release.