Benefiting from their responsiveness and adaptability, the stimuli-responsive polymers have been widely investigated and exploited in the various fields, such as environmental monitoring, ...electronics, photonics, controlled drug delivery, medical imaging and diagnostics. These potential applications have greatly promoted the development of advanced functional materials, and meanwhile set higher requirements for the smart materials in the aspects of the spatial structures, diverse linkages and variable functions. However, the linear functional polymers can not satisfy all the requirements of the multi-dimensional molecular design and acute sensitiveness due to the architectural limitation. Accordingly, stimuli-responsive hyperbranched polymers (HBPs) have been drawing more and more attention in recent years owing to their unique globular void-containing topological structure featured with a large number of terminal functional groups and branches, lower solution or melt viscosity, and better solubility. Therefore, design and synthesis of stimuli-responsive HBPs provide a robust tool for controlling the structure transition and creating the hierarchical sensitivity driven by different triggers. In this review, the developments and recent advances of preparation procedures, performance control and promising applications of various stimuli-responsive HBPs have been comprehensively summarized. Besides, the developing trend of stimuli-responsive HBPs is also discussed. It can be found that stimuli-responsive HBPs with different synthetic strategies and diverse performances have manifested more and more versatile applications.
Hyperbranched polymers (HBPs), an important subclass of dendritic macromolecules, are highly branched, three-dimensional globular nanopolymeric architectures. Attractive features like highly branched ...topological structures, adequate spatial cavities, numerous terminal functional groups and convenient synthetic procedures distinguish them from the available polymers (the linear, branched, and crosslinking polymers). Due to their unique physical/chemical properties, applications of HBPs have been explored in a large variety of fields. In particular, HBPs exhibit unique advantages in the biological and biomedical systems and devices. Firstly, the way to prepare HBPs usually only involves simple one-pot reactions and avoids the complicated synthesis and purification procedures, which makes the manufacturing process more convenient, thus reducing production costs. Secondly, the large number of end-groups of HBPs provides a platform for conjugation of the functional moieties and can also be employed to tailor-make the properties of HBPs, enhancing their versatility in biological applications. Thirdly, HBPs possess excellent biocompatibility and biodegradability, controlled responsive nature, and ability to incorporate a multiple array of guest molecules through covalent or noncovalent approaches. All of these features of HBPs are of great significance for designing and producing biomaterials. To date, significant progress has been made for the HBPs in solving some of the fundamental and technical questions toward their bioapplications. The present review highlights the contribution of HBPs to biological and biomedical fields with intent to aid the researchers in exploring HBPs for bioapplications.
Cancer cells in hypoxic tumors are remarkably resistant to photodynamic therapy. Here, we hypothesize that an oxygen and Pt(II) self-generating multifunctional nanocomposite could reverse the ...hypoxia-triggered PDT resistance. The nanocomposite contains Pt(IV) and chlorin e6, in which upconversion nanoparticles are loaded to convert 980 nm near-infrared light into 365 nm and 660 nm emissions. Upon accumulation at the tumor site, a 980 nm laser is used to trigger the nanocomposite to generate O
for consumption in the PDT process and to produce cytotoxic reactive oxygen species. The composite also releases active Pt(II) for synergistic photo-chemo therapy to enhance antitumor efficiency. The oxygen and Pt(II) self-generating prodrug is shown to have high potential to inhibit tumors out of the range of UV light, to overcome the hypoxia-triggered PDT resistance and significantly improve anticancer efficacy by the synergistic PDT-chemotherapy.
Chiral α-aryl glycines play a key role in the preparation of some bioactive products, however, their catalytic asymmetric synthesis is far from being satisfactory. Herein, we report an efficient ...nickel-catalyzed asymmetric hydrogenation of N-aryl imino esters, affording chiral α-aryl glycines in high yields and enantioselectivities (up to 98% ee). The hydrogenation can be conducted on a gram scale with a substrate/catalyst ratio of up to 2000. The obtained chiral N-p-methoxyphenyl α-aryl glycine derivatives are not only directly useful chiral secondary amino acid esters but can also be easily deprotected by treatment with cerium ammonium nitrate for further transformations to several widely used molecules including drug intermediates and chiral ligands. Formation of a chiral Ni-H species in hydrogenation is detected by
H NMR. Computational results indicate that the stereo selection is determined during the approach of the substrate to the catalyst.
Hyperbranched polymers (HBPs) are highly branched macromolecules with a three‐dimensional dendritic architecture. Due to their unique topological structure and interesting physical/chemical ...properties, HBPs have attracted wide attention from both academia and industry. In this paper, the recent developments in HBP self‐assembly and their biomedical applications have been comprehensively reviewed. Many delicate supramolecular structures from zero‐dimension (0D) to three‐dimension (3D), such as micelles, fibers, tubes, vesicles, membranes, large compound vesicles and physical gels, have been prepared through the solution or interfacial self‐assembly of amphiphilic HBPs. In addition, these supramolecular structures have shown promising applications in the biomedical areas including drug delivery, protein purification/detection/delivery, gene transfection, antibacterial/antifouling materials and cytomimetic chemistry. Such developments promote the interdiscipline researches among surpramolecular chemistry, biomedical chemistry, nanotechnology and functional materials.
Hyperbranched polymers have demonstrated great potential as excellent precursors in supramolecular self‐assembly, and many delicate supramolecular structures from zero‐dimension to three‐dimension have been prepared, such as micelles, fibers, tubes, vesicles, membranes, large compound vesicles and so on. They have displayed promising applications in the biomedical areas including drug delivery, protein purification/detection/delivery, gene transfection, antibacterial/antifouling materials and cytomimetic chemistry.
All drugs for cancer therapy face several transportation barriers on their tortuous journey to the action sites. To overcome these barriers, an effective drug delivery system for cancer therapy is ...imperative. Here, we develop a drug self-delivery system for cancer therapy, in which anticancer drugs can be delivered by themselves without any carriers. To demonstrate this unique approach, an amphiphilic drug-drug conjugate (ADDC) has been synthesized from the hydrophilic anticancer drug irinotecan (Ir) and the hydrophobic anticancer drug chlorambucil (Cb) via a hydrolyzable ester linkage. The amphiphilic Ir-Cb conjugate self-assembles into nanoparticles in water and exhibits longer blood retention half-life compared with the free drugs, which facilitates the accumulation of drugs in tumor tissues and promotes their cellular uptake. A benefit of the nanoscale characteristics of the Ir-Cb ADDC nanoparticles is that the multidrug resistance (MDR) of tumor cells can be overcome efficiently. After cellular internalization, the ester bond between hydrophilic and hydrophobic drugs undergoes hydrolysis to release free Ir and Cb, resulting in an excellent anticancer activity in vitro and in vivo.
Combinatorial antitumor therapies using different combinations of drugs and genes are emerging as promising ways to overcome drug resistance, which is a major cause for the failure of cancer ...treatment. However, dramatic pharmacokinetic differences of drugs greatly impede their combined use in cancer therapy, raising the demand for drug delivery systems (DDSs) for tumor treatment. By employing fluorescent dithiomaleimide (DTM) as a linker, we conjugate two paclitaxel (PTX) molecules with a floxuridine (FdU)‐integrated antisense oligonucleotide (termed chemogene) to form a drug–chemogene conjugate. This PTX–chemogene conjugate can self‐assemble into a spherical nucleic acid (SNA)‐like micellular nanoparticle as a carrier‐free DDS, which knocks down the expression of P‐glycoprotein and subsequently releases FdU and PTX to exert a synergistic antitumor effect and greatly inhibit tumor growth.
A carrier‐free drug delivery system is assembled using an amphiphilic drug–chemogene conjugate, which is prepared by conjugating two paclitaxel (PTX) molecules with a floxuridine‐integrated antisense oligonucleotide against P‐glycoprotein (termed chemogene) using a fluorescent dibromomaleimide linker. The PTX–chemogene assembly can effectively reverse drug resistance and inhibit tumor growth.
Photo-responsive polymeric micelles have received increasing attention in both academic and industrial fields due to their efficient photo-sensitive nature and unique nanostructure. In view of the ...photo-reaction mechanism, photo-responsive polymeric micelles can be divided into five major types: (1) photoisomerization polymeric micelles, (2) photo-induced rearrangement polymeric micelles, (3) photocleavage polymeric micelles, (4) photo-induced crosslinkable polymeric micelles, and (5) photo-induced energy conversion polymeric micelles. This review highlights the recent advances of photo-responsive polymeric micelles, including the design, synthesis and applications in various biomedical fields. Especially, the influence of different photo-reaction mechanisms on the morphology, structure and properties of the polymeric micelles is emphasized. Finally, the possible future directions and perspectives in this emerging area are briefly discussed.
Up to now, limited tumor penetration and poor therapeutic efficiency of drug-loaded nanoparticles are still the major challenges in nanomedicines for cancer chemotherapy. In photodynamic therapy, ...photosensitizers are often used to generate cytotoxic reactive oxygen species to kill cancer cells. Here, we report a kind of ROS-responsive nanoparticles with light-triggered size-reducing for enhanced tumor penetration and in vivo drug delivery to improve therapeutic efficiency. The nanoparticles were constructed by the self-assembly of an amphiphilic hyperbranched polyphosphoester containing thioketal units and photosensitizers, which is synthesized through the self-condensing ring-opening polymerization of a novel cyclic phosphate monomer and then end-capped with photosensitizer Chlorin e6. These nanoparticles have an initial averaged diameter of ∼210 nm, which can be used as drug carriers to load camptothecin with relatively stable in blood circulation. The CPT-loaded nanoparticles can be concentrated in tumor tissues through the long blood circulation and enhanced permeability and retention effect. Upon 660 nm laser irradiation on tumor tissues, the Ce6s in nanoparticles can effectively generate ROS to kill cancer cells meanwhile cleave the thioketal units to sequentially reduce the size of nanoparticles, which facilitate them more efficient tumor penetration with a programmable release of CPT. Both in vitro and in vivo studies confirmed the above results. Such ROS-responsive nanoparticles with light-triggered size-reducing provided a feasible approach to improve drug tumor penetration and achieve satisfied therapeutic efficacy.
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Based on their structural similarity to natural nucleobases, nucleoside analogue therapeutics were integrated into DNA strands through conventional solid‐phase synthesis. By elaborately designing ...their sequences, floxuridine‐integrated DNA strands were synthesized and self‐assembled into well‐defined DNA polyhedra with definite drug‐loading ratios as well as tunable size and morphology. As a novel drug delivery system, these drug‐containing DNA polyhedra could ideally mimic the Trojan Horse to deliver chemotherapeutics into tumor cells and fight against cancer. Both in vitro and in vivo results demonstrate that the DNA Trojan horse with buckyball architecture exhibits superior anticancer capability over the free drug and other formulations. With precise control over the drug‐loading ratio and structure of the nanocarriers, the DNA Trojan horse may play an important role in anticancer treatment and exhibit great potential in translational nanomedicine.
DNA Trojan horses: An antitumor nucleoside analogue (floxuridine) is integrated into DNA strands through conventional solid‐phase synthesis. The floxuridine‐integrated DNA oligomers with precise drug‐loading ratios are assembled into DNA polyhedra, which can function as nanoscale Trojan horses to fight against cancer both in vitro and in vivo.
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