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The comprehensive evaluation of tumor vasculature that is crucial for the development, expansion, and spread of cancer still remains a great challenge, especially the three-dimensional (3D) evaluation of vasculatures. In this study, we proposed a magnetic resonance (MR) angiography strategy with interlocking stratagem of zwitterionic Gd-chelate contrast agents (PAA-Gd) for continuous monitoring of tumor angiogenesis progression in 3D. Owing to the zwitterionic structure and nanoscale molecular diameter, the longitudinal molar relaxivity (r1) of PAA-Gd was 2.5 times higher than that of individual Gd-chelates on a 7.0 T MRI scanner, resulting in the higher-resolution visualization of tumor vasculatures. More importantly, PAA-Gd has the appropriate blood half-life (69.2 min), emphasizing the extended imaging window compared to the individual Gd-chelates. On this basis, by using PAA-Gd as the contrast agent, the high-resolution, 3D depiction of the spatiotemporal distribution of microvasculature in solid tumors formed by different cell lines over various inoculation times has been obtained. This method offers an effective approach for early tumor diagnosis, development assessment, and prognosis evaluation.

Due to the extremely wide crystallization temperature range of chemically jointed PA6 blocks, three types of spherulitic morphologies were found in poly(ε-caprolactone)-b-polyamide 6-b-poly(ε-caprolactone) (PCL-b-PA6-b-PCL), including conventional ring-banded spherulites, special spherulites with a curve-like morphology, and composite spherulites with the above two characteristics. The formation conditions, internal factors, and the lamellar orientation and assembly of different spherulites have been studied in detail. It was found that the PCL spherulites with a curve-like morphology can form only when PCL and PA6 blocks crystallize simultaneously, whereas the ring-banded spherulites can form regardless of whether PA6 is amorphous or crystallized. The morphological results show that the ring-banded spherulites are composed of lamellae with different orientations along the radial direction, while spherulites with a curve-like morphology are composed of different stacked lamellae (flat-on lamellae and tilted flat-on lamellae) arranged alternately along the tangential direction. The appearance of unusual spherulitic morphology may result from different internal stress induced by chemically jointed PA6 blocks under diverse crystallization conditions.

Encryption of meaningful images into unidentifiable noise-like images can improve the security of images during storage and transmission. In this paper, a novel color image encryption method based on the lifting scheme and cross-component permutation (CIE-LSCP) is introduced. First, original image is divided into red, green and blue components, and then the three components are processed by a preprocessing strategy based on the lifting scheme (PSLS) to change the statistical distribution of the pixels. Second, a block-based cross-component permutation based on index vectors (BCPIV) is presented to divide three preprocessed components into blocks and perform the cross-component permutation operation on them, and three random matrices are utilized to determine the target component, target block and target pixel position of the current pixel to be moved, respectively. Subsequently, a multi stochastic diffusion based on random sequences (MSDRS) is developed to alter the pixel values of the permutated components, and finally a ciphertext image is gotten by merging the three components. Moreover, the SHA256 hash values of the plaintext image are used to obtain the initial parameters of the chaotic system, and the obtained chaotic sequences are applied in the image encryption process. Wherein the generated random sequences are highly reliant on the plaintext image, making the encryption scheme resistant to both known-plaintext attacks and chosen-plaintext attacks. Experimental results demonstrate that the proposed scheme has good security and effectiveness and can be applied for secure transmission of digital images over the Internet.

Various functional nanomaterials have been fabricated as diagnostic and therapeutic nanomedicines; however, the nanoparticles closely interact with proteins when immersed in biological fluids, forming a “protein corona” that critically alters the biological identity of nanomedicine. Here, we developed a robust strategy to construct theranostic nanoprobes based on protein-corona-coated Fe3O4nanoparticles and biomineralization in the corona. Water-soluble carboxylic Fe3O4nanoparticles were prepared by treating oleate-capped Fe3O4nanoparticles with Lemieux–von Rudloff reagent. Bovine serum albumin (BSA) was used as a model protein to form a corona on the surface of Fe3O4nanoparticles, endowing the Fe3O4nanoparticles with biocompatibility and nonimmunogenicity. The protein corona also provides a template for biomimetic mineralization of Fe3+with tannic acid (TA) to construct Fe3O4@BSA-TAFeIIInanoprobes. The TA-Fe(III) biominerals can not only act as photothermal therapy agents but also interact with unsaturated transferrin in plasma to form a “hybrid” corona, enabling the nanoprobes to target tumor cells through the mediation of transferrin receptors, which commonly overexpress on tumor cell membranes. Once taken in by tumor cells, the protonation of phenol hydroxyl groups in acidic lysosomes would lead to the release of Fe3+, inducing tumor cell death through a ferroptosis/apoptosis hybrid pathway. In addition, the released Fe3+can boost the T1-weighted MR imaging performance, and the Fe3O4nanoparticles serve as T2-weighted MR imaging contrast agents. It is thus believed that the current nanoprobes can realize the enhanced dual-modality MR imaging and combined therapy of tumors through controlling the protein corona and biomineralization.

Clinical radiation therapy (RT) is often hindered by the low radiation energy absorption coefficient and the hypoxic features of tumor tissues. Among the tremendous efforts devoted to overcoming the barriers to efficient RT, the application of hypoxic radiosensitizers and cell-cycle-specific chemotherapeutics has shown great potential. However, their effectiveness is often compromised by their limited bioavailability, especially in the hypoxic region, which plays a major role in radioresistance. Herein, to simultaneously improve the delivery efficacy of both hypoxic radiosensitizer and cell-cycle-specific drug, a gambogic acid (GA) metronidazole (MN) prodrug (GM) was designed and synthesized based on GA, a naturally occurring chemotherapeutic and multiple pathway inhibitor, and MN, a typical hypoxic radiosensitizer. In combination with MN-containing block copolymers, the prodrug nanosensitizer (NS) of GM was obtained. Owing to the bioreduction of MN, the as-designed prodrug could be efficiently delivered to hypoxic cells and act on mitochondria to cause the accumulation of reactive oxygen species. The strong G2/M phase arrest caused by the prodrug NS could further sensitize treated cells to external radiation under hypoxic conditions by increasing DNA damage and delaying DNA repair. After coadministration of the NS with a well-established tissue-penetrating peptide, efficient tumor accumulation, deep tumor penetration, and highly potent chemoradiotherapy could be achieved.

Polyesteramides have attracted much attention due to their intriguing properties. However, the synthesis of di- or triblock polyesteramides based on polyamide 6 (PA6) remains challenging owing to their harsh reaction conditions. In this work, we introduced a new strategy to synthesize poly(ε-caprolactone)-block-PA6-block-poly(ε-caprolactone) (PCL-b-PA6-b-PCL) in a mild way. A series of well-designed copolymers were characterized by gel permeation chromatography, 1H, DOSY, and 13C NMR, and their crystallization and melting behavior, degradation rate, and compatibilization effect on PA6/PCL blends were found to be strongly composition dependent. Interestingly, the copolymers exhibited diverse spherulite morphologies, including curving stems and banded spherulites, which also correlated with the different relative content of PA6. Besides, PA6 nanodomains could act as physical cross-linking points to improve the tensile strength and Young’s modulus of PCL. This work fills the synthesis gap of well-defined PA6-based triblock polyesteramides, providing new materials for material modification and elucidation of some basic scientific questions.

With the advancement of multimedia technology and coming of big data era, the size of image data is significantly increased. However, the traditional image encryption methods cannot solve the emerging problems of efficient compression. To settle with this challenge, an effective content-adaptive image compression and encryption method based on compressive sensing and double random phase encoding (DRPE) is proposed in this paper. The original image is converted to one low-frequency part and three high-frequency parts by DWT and then permutated by sorting-based chaotic sequences. Afterward, a novel measurement matrix optimization algorithm based on adaptive step size is presented to measure the high-frequency components. To enhance the security of the scheme, the DRPE, quantization, and diffusion are successively performed on the complex matrix composed of the shuffled low-frequency component and three measurement value matrices to obtain the cipher image. Logistic-Sine chaotic system is utilized to produce the chaotic keystreams for the encryption process, and its system parameter and initial value are determined by the information entropy of the plain image and external key parameters, so that the proposed cipher can withstand known-plaintext and chosen-plaintext attacks effectively. Numerical experiments demonstrate the effectiveness of the proposed image compression and encryption algorithm.

Postoperative radiotherapy currently stands as the cornerstone of glioblastoma (GBM) treatment. Nevertheless, low-dose radiotherapy has been proven ineffective for GBM, due to hypoxia in the GBM microenvironment, which renders the resistance to radiation-induced cell death. Moreover, the overexpression of the PLK1 gene in glioma cells enhances GBM proliferation, invasion, metastasis, and resistance to radiation. This study introduced a hybrid membrane-camouflaged biomimetic lipid nanosensitizer (CNL@miPA), which efficiently encapsulated gold nanoclusters (PA) and miR-593–5p by a chimeric membrane derived from lipids, cancer cells, and natural killer cells. CNL@miPA exhibited exceptional blood-brain barrier and tumor tissue penetration, effectively ameliorating hypoxia and synergizing with radiotherapy. By enabling prolonged miRNA circulation in the bloodstream and achieving high enrichment at the tumor site, CNL@miPA significantly suppressed tumor growth in combination treatment, thereby significantly extending the survival period of treated mice. Overall, the developed biomimetic nanosensitizer represented an efficient and multifunctional targeted delivery system, offering a novel strategy for gene-radiotherapy of GBM.

Nanoparticles are attractive platforms for the delivery of various anticancer therapeutics. Nevertheless, their applications are still limited by the relatively low drug loading capacity and the occurrence of multidrug resistance (MDR) against chemotherapeutics. In this study, we report that the integration of d-α-tocopherol succinate (VES) residue with both chitosan and paclitaxel (PTX) led to significant improvement of drug loading capacity and drug loading efficiency through the enhancement of drug/carrier interaction. After the incorporation of hyaluronic acid containing PEG side chains (HA-PEG), higher serum stability and more efficient cellular uptake were obtained. Due to HA coating, VES residues and the enzymatic responsive drug release property, such facile nanoparticles actively targeted cancer cells that overexpress CD44 receptor and efficiently reversed the MDR of treated cells, but caused no significant toxicity to mouse fibroblast (NIH-3T3). More importantly, with HA-PEG coating, longer blood circulation and more effective tumor accumulation were achieved for prodrug nanoparticles. Finally, superior anticancer activity and excellent safety profile was demonstrated by HA-PEG coated enzymatically activatable prodrug nanoparticles compared to commercially available Taxol formulation.

Shape memory polymers (SMPs) responsive to various external stimuli can realize a complex shape transformation process and have attracted extensive attention. However, integrating multiple stimulus-responsive mechanisms in one material often requires a complex molecular design and synthesis procedure. In this work, we designed a novel dual-responsive heterogeneous hydrogel (PU–PAM/Alg/PDA), which was manufactured through in situ free radical polymerization of acrylamide (AM) in the presence of alginate (Alg) and polydopamine (PDA) in a porous polycaprolactone-based polyurethane foam (PU-foam). The PU–PAM/Alg/PDA hydrogel could achieve thermal responsiveness through melting-crystallization transformation of polycaprolactone (PCL), while the metallo-supramolecular interactions between Alg and Fe3+could provide ion responsiveness for this hydrogel. This dual-programmable feature endowed the heterogeneous hydrogel with a complex shape-morphing behavior and also a reconfiguration ability for the permanent shape. Meanwhile, the strong hydrogen bondings between PDA and polyurethane chains enhanced the interfacial adhesions, resulting in the structural integrity and excellent mechanical property of PU–PAM/Alg/PDA. The in vitro and in vivo tests revealed the good biocompatibility of the heterogeneous hydrogel, and the potential of the heterogeneous hydrogel as an esophageal stent was evaluated in vitro as conceptual proof.

In this study, maleic anhydride-modified lignin (LG-M), a ROS-cleavable thioketal (TK) bond, and polyethylene glycol (PEG) were used to synthesize a lignin-based copolymer (LG-M(TK)-PEG). Doxorubicin (DOX) was attached to the ROS-cleavable bond in the LG-M(TK)-PEG for the preparation of the ROS-activatable DOX prodrug (LG-M(TK-DOX)-PEG). Nanoparticles (NPs) with a size of 125.7 ± 3.1 nm were prepared by using LG-M(TK-DOX)-PEG, and they exhibited enhanced uptake by cancer cells compared to free DOX. Notably, the presence of lignin in the nanoparticles could boost ROS production in breast cancer 4T1 cells while showing little effect on L929 normal cells. This selective effect facilitated the specific activation of the DOX prodrug in the tumor microenvironment, resulting in the superior tumor inhibitory effects and enhanced biosafety relative to free DOX. This work demonstrates the potential of the LG-M(TK-DOX)-PEG NPs as an efficient drug delivery system for cancer treatment.

A tumour microenvironment imposes barriers to the passive diffusion of molecules, which renders tumour penetration an unresolved obstacle to an effective anticancer drug delivery. Here, we present a γ-glutamyl transpeptidase-responsive camptothecin–polymer conjugate that actively infiltrates throughout the tumour tissue through transcytosis. When the conjugate passes on the luminal endothelial cells of the tumour blood vessels or extravasates into the tumour interstitium, the overexpressed γ-glutamyl transpeptidase on the cell membrane cleaves the γ-glutamyl moieties of the conjugate to generate positively charged primary amines. The resulting cationic conjugate undergoes caveolae-mediated endocytosis and transcytosis, which enables transendothelial and transcellular transport and a relatively uniform distribution throughout the tumour. The conjugate showed a potent antitumour activity in mouse models that led to the eradication of small solid tumours (~100 mm3) and regression of large established tumours with clinically relevant sizes (~500 mm3), and significantly extended the survival of orthotopic pancreatic tumour-bearing mice compared to that with the first-line chemotherapeutic drug gemcitabine. A zwitterionic camptothecin–polymer conjugate that is enzymatically transformed in a cationic molecule at the tumour periphery penetrates deep into tumours via caveolae-mediated endocytosis and transcytosis, resulting in high anticancer efficiency in vivo.

Efficient tumor accumulation and body clearance are two paralleled requirements for ideal nanomedicines. However, it is hard for both to be met simultaneously. The inefficient clearance often restrains the application of drug delivery systems (DDSs), especially for high-dosage administration. In this study, the star-like and block structures are combined to enhance the tumor specific targeting of the parent structures and obtain additional renal excretion property. The influences of polymer architectures and chemical compositions on the physicochemical and biological properties, particularly the simultaneous achievement of tumor accumulation and renal clearance, have been investigated. Among the tested conjugates, an eight-arm triblock star polymer based on poly(ethylene glycol) (PEG) and poly(N-(2-hydroxyl) methacrylamide) (PHPMA) is found to simultaneously fulfill the requirements of superior tumor accumulation and efficient renal clearance due to the appropriate micelle size and reversible aggregation process. On the basis of this conjugate, 60 mg/kg of Dox equivalent (much higher than the maximum tolerated dose (MTD) of Dox) can be administered to efficiently suppress tumor growth without causing any obvious toxicity. This work provides a new approach to design polymer–drug conjugates for tumor specific application, which can simultaneously address the efficacy and safety concerns.

Ubiquitin specific peptidase 39 (USP39), an essential factor in the assembly of the mature spliceosome complex, has an aberrant expression in several cancer. However, its function and the corresponding mechanism on human osteosarcoma has not been fully explored yet. The mRNA and DNA copies of USP39 were increased in osteosarcoma cancer tissues compared with the one in human normal tissues according to datasets from the publicly available Oncomine database. A further western blot analysis also demonstrated an aberrant endogenous expression of USP39 in three different osteosarcoma cells. Then lentivirus-mediated short hairpin RNA (shRNA) was designed to silence USP39 in human osteosarcoma cell line U2OS, which is used to test the impact of USP39-silencing on cellular proliferation, colony formation, cell cycle distribution and apoptosis. Knockdown of USP39 expression in U2OS cell significantly decreased cell proliferation, impaired colony formation ability. A further analysis indicated suppression of USP39 arrested cell cycle progression at G2/M phase via p21 dependent way. In addition, the results of Annexin V/7-AAD staining suggested the knockdown of USP39 could promote U2OS cell apoptosis through PARP cleavage. These results uncover the critical role of USP39 in regulating cancer cell mitosis and indicate USP39 is critical for osteosarcoma tumorigenesis.

The formation and development of cancer is usually accompanied by angiogenesis and is related to multiple pathways. The inhibition of one pathway by monotherapy might result in the occurrence of drug resistance, tumor relapse, or metastasis. Thus, a combinatory therapeutic system that targets several independent pathways simultaneously is preferred for the treatment. To this end, we prepared combinatory drug delivery systems consisting of cytotoxic drug SN38, pro-apoptotic KLAK peptide, and survivin siRNA with high drug loading capacity and reductive responsiveness for the treatment of multi-drug-resistant (MDR) cancer. With the help of positive charge and the synergistic effect of different drug, the combinatory systems inhibited the growth of doxorubicin-resistant breast cancer cells (MCF-7/ADR) efficiently. Interestingly, the systems without siRNA showed more superior in vivoanticancer efficacy than those with siRNA which exhibited enhanced in vitrocytotoxicity and pro-apoptotic ability. This phenomenon could be attributed to the preferential tumor accumulation, strong tumor penetration, and excellent tumor vasculature targeting ability of the combinatory micelles of SN38 and KLAK. As a result, a combinatory multitarget therapeutic system with positive charge induced tumor accumulation and vasculature targeting which can simultaneously inhibit the growth of both tumor cell and tumor vasculature was established. This work also enlightened us to the fact that the design of combinatory drug delivery systems is not just a matter of simple drug combination. Besides the cytotoxicity and pro-apoptotic ability, tumor accumulation, tumor penetration, or vascular targeting may also influence the eventual antitumor effect of the combinatory system.

Aims and background Interleukin-6 (IL-6) has been shown to promote tumor survival, metastasis, and angiogenesis, in addition to possessing antitumor activities. In light of the conflicting data, we sought to determine whether IL-6 could be used as a prognostic factor for patients with breast cancer.Methods Eligible studies describing the use of IL-6 as a prognostic factor for breast cancer were identified. Data describing overall survival (OS), disease-free survival (DFS), and clinicopathologic features were collected and analyzed.Results Thirteen articles containing 3,224 breast cancer patients were identified. The results showed that IL-6 expression was not associated with lymph node metastasis, tumor size, or histologic grade. Moreover, there was no correlation between IL-6 expression and DFS. However, the combined hazard ratio (95% confidence interval) for OS was 2.15 (1.46, 3.17). Sensitivity analysis further demonstrated that, for OS, the results of this meta-analysis were stable. A subgroup analysis showed that the source used to detect IL-6 levels may have altered the pooled results for OS.Conclusions Taken together, these results indicate that IL-6 expression is associated with poor prognosis for breast cancer and the prognostic role is affected by the source used to detect IL-6 levels.

Near-infrared (NIR) light-triggered shape memory polymers are expected to have a more promising prospect in biomedical applications compared with traditional heat-triggered shape memory polymers. In this work, a new kind of polyurethane with NIR light-triggered shape memory property was prepared by using polycaprolactone (PCL), polydopamine nanoparticles (PDANPs), hexamethylene diisocyanate (HDI), and 1,4-butanediol (BDO). The synthesized PCL–PDA polyurethanes, especially when the weight content of PDANPs was 0.17%, showed excellent mechanical properties because the PDANPs were well-dispersed in polyurethanes by the chain extension reaction. Moreover, it also showed an NIR light-triggered rapid shape recovery because of the photothermal effect of polydopamine. The in vitro and in vivo tests showed that the PCL–PDA polyurethane would not inhibit cell proliferation nor induce a strong host inflammatory response, revealing the non-cytotoxicity and good biocompatibility of the material. In addition, the PCL–PDA polyurethane exhibited excellent in vivo NIR light-triggered shape memory performance under an 808 nm laser with low intensity (0.33 W cm–2), which was harmless to the human skin. These results demonstrated the potential of the PCL–PDA polyurethane in biomedical implant applications.

A double template method to fabricate poly(ε-caprolactone) (PCL) hierarchical patterned nanowires with highly ordered nano- and microscaled topography was developed in this study. The topography of PCL film with a patterned nanowire surface can be easily and well controlled by changing the template and melting time of PCL film on the templates. The surface morphology, water contact angle, protein adsorption, and cell growth behavior on the PCL films with different surface structures were well studied. The results revealed that the PCL nanowire arrays and the hierarchical patterned nanowires showed higher capability of protein adsorption and better cell growth than the PCL film with smooth surface. Typically, the PCL surface with hierarchical nanowire patterns was most favorable for cell attachment and proliferation. The present study was innovative at fabrication of polymer substrates with hierarchical architecture of nanowires inside microscaled islands to gain insight into the cell response to this unique topography and to develop a new method of constructing the bionic surface for tissue engineering applications.

Abstract: In situ evaluation of cell cultivation on degrading poly(ɛ-caprolactone) (PCL) films was studied. New culture surroundings were constructed for cell growth by using PCL films as substrates and adding Pseudomonas cepacia lipase to accelerate biodegradation of PCL films. MTT experiments for 10 h indicated the low cytotoxicity of lipase solution with concentration up to 0.2 mg/mL for MG-63 cells growth on PCL films. With the optimized lipase concentration and degradation time, we studied cell growth behavior on dynamically changed PCL films by adding lipase to the culture surroundings. MTT, fluorescence microscopy and scanning electron microscopy (SEM) were used to evaluate cell viability, proliferation and morphologies. It was found that cell viability and proliferation were not affected by the added lipase solution negatively. In contrast, cells cultured on degrading PCL films showed good growth behavior with clear fusiform shape and pseudopods. Importantly, the enzymatic degradation of PCL films with cells attachment showed distinctive morphology compared to the degradation in lipase solution without cells. The simultaneous cell growth and PCL film degradation were well discussed in this work, which may better understand the interaction between cell growth and polymer degradation.

Abstract: A series of controllable amphiphilic block copolymers composed of poly(ethylene oxide) (PEO) as the hydrophilic block and poly(ɛ-caprolactone) (PCL) as the hydrophobic block with the amino terminal group at the end of the PEO chain (PCL-b-PEO-NH2) were synthesized. Based on the further reaction of reactive amino groups, diblock copolymers with functional carboxyl groups (PCL-b-PEO-COOH) and functional compounds RGD (PCL-b-PEO-RGD) as well as the triblock copolymers with thermosensitive PNIPAAm blocks (PCL-b-PEO-b-PNIPAAM) were synthesized. The well-controlled structures of these copolymers with functional groups and blocks were characterized by gel permeation chromatography (GPC) and 1H NMR spectroscopy. These copolymers with functionalized hydrophilic blocks were fabricated into microspheres for the examination of biofunctions via cell culture experiments and in vitro drug release. The results indicated the significance of introducing functional groups (e.g., NH2, COOH and RGD) into the end of the hydrophilic block of amphiphilic block copolymers for biomedical potentials in tissue engineering and controlled drug release.

A series of amphiphilic graft copolymers of polyethylene glycolcoglycidolgraftcaprolactone PEGcoPGLgPCL with PEG as the hydrophilic backbone chain and hydrophobic PCL as side chains have been synthesized by living anionic polymerization and ringopening polymerization. By changing the composition of the PEGcoPGL backbone chains, and the molar ratio of CL monomer to PEGcoPGL in the feed, copolymers with welldefined architecture and controllable numbers and length of graft chains can be obtained. The micellization and drug release of the PEGcoPGLgPCL graft copolymers have been studied in terms of dependence on graft numbers and length, and the results indicate that the micelles with shorter PCL side chains have more compact cores and a relatively small size which are favorable for drug loading and controlled release.

The melting behavior, crystal structure, and spherulitic morphology of melt-crystallized poly(butylene adipate) (PBA) at a temperature range from 25 to 35 °C have been investigated by differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD) and optical microscopy. Two distinct melting behaviors with double peaks have been observed after melt-crystallizing at different temperatures. X-ray analysis proves that these two behaviors arise from two forms of PBA crystal structures. The β-form crystals are formed at temperatures below 31 °C, while the α-form crystals are formed above 29 °C. When the crystallization temperature is 30 ± 1 °C, a mixture of α-form and β-form crystals has been formed. The influences of annealing treatment and sample preparation method on the two forms of PBA crystal structures have been discussed. The results indicate that the low temperature-formed β-form crystals are very sensitive to the preparation conditions. The melting curves at different heating rates for poly(butylene adipate) after melt-crystallized at 25 °C and 33 °C, respectively.

Well-defined block copolymers of L-lactide-b-e-caprolactone were synthesized by sequential polymerization using a rare earth complex, Y(CF3COO)3/Al(iso-Bu)3, as catalyst system. The compositions of the block copolymers could be adjusted by manipulating the feeding ratio of comonomers. The characterizations by GPC, 1H NMR, 13C NMR, and DSC displayed that the block copolymer, poly(e-caprolactone-b-L-lactide) [P(CL-b-LLA)], had a narrow molecular weight distribution and well-controlled sequences without random placement.

The nonisothermal crystallization behavior and melting process of the poly(ε-caprolactone) (PCL)/poly(ethylene oxide) (PEO) diblock copolymer in which the weight fraction of the PCL block is 0.80 has been studied by using differential scanning calorimetry (DSC). Only the PCL block is crystallizable, the PEO block with 0.20 weight fraction cannot crystallize. The kinetics of the PCL/PEO diblock copolymer under nonisothermal crystallization conditions has been analyzed by Ozawa's equation. The experimental data shows no agreement with Ozawa's theoretical predictions in the whole crystallization process, especially in the later stage. A parameter, kinetic crystallinity, is used to characterize the crystallizability of the PCL/PEO diblock copolymer. The amorphous and microphase separating PEO block has a great influence on the crystallization of the PCL block. It bonds chemically with the PCL block, reduces crystallization entropy, and provides nucleating sites for the PCL block crystallization. The existence of the PEO block leads to the occurrence of the two melting peaks of the PCL/PEO diblock copolymer during melting process after nonisothermal crystallization. The comparison of nonisothermal crystallization of the PCL/PEO diblock copolymer, PCL/PEO blend, and PCL and PEO homopolymers has been made. It showed a lower crystallinity of the PCL/PEO diblock copolymer than that of others and a faster crystallization rate of the PCL/PEO diblock copolymer than that of the PCL homopolymer, but a slower crystallization rate than that of the PCL/PEO blend. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 63: 1793–1804, 1997

A novel rare earth coordination system composed of lanthanide trifluoroacetates Ln(CF3COO)3 (Ln=Y, Yb, Nd, Tm, Ho, La, Pr) and tri‐isobutylaluminium Al(i‐Bu)3 was used as catalyst for the polymerization of ɛ-caprolactone (CL), D,L-lactide (DLLA) and their copolymerization. The influence of temperature, time and catalyst concentration on polymerization yields and molecular weights of the polyesters have been studied. It was shown that the ring‐opening polymerization of cyclic esters catalysed by Ln(CF3COO)3/Al(i‐Bu)3 has some living character and the molecular weight of the polyester could be controlled by adjusting the molar ratio of monomer to catalyst. The DLLA/CL copolymer was synthesized by sequential addition of monomers and the structure of the copolyester was characterized by GPC, NMR and DSC. © 1998 SCI.

Chemotherapy is one of the most commonly used clinical antitumor strategies. However, the therapy-induced proliferative burst, which always accompanies drug resistance and metastasis, has become a major obstacle during treatment. Except for some endogenous cellular or genetic mechanisms and some microenvironmental selection pressures, the intercellular connections in the tumor microenvironment (TME) are also thought to be the driving force for the acquired drug resistance and proliferative burst. Even though some pathway inhibitors or cell exempting strategies could be applied to partially avoid these unwanted communications, the complexity of the TME and the limited knowledge about those unknown detrimental connections might greatly compromise the efforts. Therefore, a more broad-spectrum strategy is urgently needed to relieve the drug-induced burst proliferation during various treatments. In this article, based on the possible discrepancies in metabolic activity between cells with different growth rates, several ester-bond-based prodrugs were synthesized. After screening, 7-ethyl-10-hyodroxycamptothecin-based prodrug nanoparticles were found to efficiently overcome the paclitaxel resistance, to selectively act on the malignantly proliferated drug-resistant cells and, furthermore, to greatly diminish the proliferative effect of common cytotoxic agents by blocking the detrimental intercellular connections. With the discriminating ability against malignant proliferating cells, the as-prepared prodrug nanomedicine exhibited significant anticancer efficacy against both drug-sensitive and drug-resistant tumor models, either by itself or by combining with highly potent nonselective chemotherapeutics. This work provides a different perspective and a possible solution for the treatment of therapy-induced burst proliferation.