The development of novel drug delivery systems is an essential step toward controlled site-specific administration of therapeutics within the body. It is desirable for delivery vehicles to be introduced into the body ...The development of novel drug delivery systems is an essential step toward controlled site-specific administration of therapeutics within the body. It is desirable for delivery vehicles to be introduced into the body through minimally invasive means and, these vehicles should be capable of releasing drug to their intended location at a controlled rate. Furthermore, it is desirable to develop drug delivery systems that are capable of in vivo to suffer degradation and to deliver the drug completely, avoiding the need to surgically remove the vehicle at the end of its useful lifetime. Hydrogels are of particular interest for drug delivery applications due to their ability to address these needs in addition to their good biocompatibility, tunable network structure to control the diffusion of drugs and, tunable affinity for drugs. However, hydrogels are also limited for drug delivery applications due to the often quick elution of drug from their highly swollen polymer matrices as well as the difficulty inherent in the injection of macroscopic hydrogels into the body. This paper presents an overview to the advances in hydrogels based drug delivery. Different types of hydrogels can be used for drug delivery to specific sites in the gastrointestinal tract ranging from the oral cavity to the colon. These novel systems exhibit a range of several peculiar properties which make them attractive as controlled drug release formulations. Moreover, such materials are biocompatible and can be formulated to give controlled, pulsed, and triggered drug release profiles in a variety of tissues.展开更多
Subcellular organelle-specific nanoparticles for simultaneous tumor targeting, imaging, and drug delivery are of enormous interest in cancer therapy. Herein, we report a selective mitochondria-targeting probe 1, which...Subcellular organelle-specific nanoparticles for simultaneous tumor targeting, imaging, and drug delivery are of enormous interest in cancer therapy. Herein, we report a selective mitochondria-targeting probe 1, which was synthesized by incorporating a triphenyl phosphine with a cyanostilbene and a long alkyl chain moiety. Probe 1 was found to display fluorescence via aggregation-induced emission （AIE）. The low molecular-weight cyanostilbene-based probe 1, with and without an anticancer drug, formed a narrow homogeneous nanorod with ca. 110 nm of length or nanopartides with ca. 20 nm diameter in aqueous media. The self-assembled cyanostilbene nanoparticles （N1） selectively accumulated in the mitochondria of cancer cells and emitted fluorescence. N1 was also able to deliver an anticancer drug, doxorubicin （DOX）, to the mitochondria with high efficiency. More importantl~ N1 exhibited highly selective cytotoxicity for cancer cells over normal cells. The great potential applications of this self-assembled nanoparticle to biological systems result from its ability to aggregate in the mitochondria. This aggregation led to a significant increase in the generation of intraceUular reactive oxygen species and to a decrease in the mitochondrial membrane potential in cancer cells. Furthermore, tumor tissue uptake experiments in mice proposed that the self-assembled N1 had the ability to internalize and deliver the anticancer drug into tumor tissues effectively. Moreover, both N1 and Nl-encapsulated doxorubicin （N1-DOX） effectively suppressed tumor growth in a xenograft model in vivo. Taken together, our findings indicate that applications of N1 as a mitochondrial targeting probe, drug delivery platform, and chemotherapeutic agent provide a unique strategy for potential image-guided therapy as well as a site-specific delivery system to cancer cells.展开更多
Recently, covalent-organic polymers （COPs）, which covalently cross-link different types of organic molecules to form organic network structures, have received significant attention in various fields. However, the de...Recently, covalent-organic polymers （COPs）, which covalently cross-link different types of organic molecules to form organic network structures, have received significant attention in various fields. However, the design of COPs that allows them to act as therapeutic agents remains to be explored. In the present study, a new class of COPs was fabricated by cross-linking the photosensitizer meso-tetra（p-hydroxyphenyl） porphine （THPP） to a chemotherapeutic pro-drug, cis-platinum （IV）; the latter also acts as a reduction-responsive linker. After further conjugation with polyethylene glycol （PEG） in this one-pot reaction, we obtained THPP-Pt-PEG COPs, which can be stored in a lyophilized form and occur as stable nanoparticles in aqueous solution. The THPP-Pt-PEG COPs are effective in killing cancer cells through photodynamic treatment, and exhibited reduction-responsive degradation/drug release behaviors. Upon intravenous injection, the COPs, with a long blood circulation time, showed efficient tumor accumulation. Interestingly, we revealed that after injection of THPP-Pt-PEG COPs, tumors on mice exhibited greatly improved vascular perfusion and largely relieved tumor hypoxia, which favored subsequent photodynamic treatment. Hence, the combined chemo-photodynamic therapy of the COPs offers a remarkably improved therapeutic outcome compared to that with mono-therapies. This work presents a COP-based nanomedicine with high drug loading, lyophilizable formulation, prolonged blood half-life, efficient tumor passive homing, inherent biodegradability, and multiple therapeutic functions to achieve enhanced cancer combination therapy, with promise for clinical translation.展开更多
基金This work was financially supported by a Grant(Praxis SFRH/BD/48324/2008)from FCT(Fundacao para a Ciencia e a Tecnologia,Portugal).
文摘The development of novel drug delivery systems is an essential step toward controlled site-specific administration of therapeutics within the body. It is desirable for delivery vehicles to be introduced into the body through minimally invasive means and, these vehicles should be capable of releasing drug to their intended location at a controlled rate. Furthermore, it is desirable to develop drug delivery systems that are capable of in vivo to suffer degradation and to deliver the drug completely, avoiding the need to surgically remove the vehicle at the end of its useful lifetime. Hydrogels are of particular interest for drug delivery applications due to their ability to address these needs in addition to their good biocompatibility, tunable network structure to control the diffusion of drugs and, tunable affinity for drugs. However, hydrogels are also limited for drug delivery applications due to the often quick elution of drug from their highly swollen polymer matrices as well as the difficulty inherent in the injection of macroscopic hydrogels into the body. This paper presents an overview to the advances in hydrogels based drug delivery. Different types of hydrogels can be used for drug delivery to specific sites in the gastrointestinal tract ranging from the oral cavity to the colon. These novel systems exhibit a range of several peculiar properties which make them attractive as controlled drug release formulations. Moreover, such materials are biocompatible and can be formulated to give controlled, pulsed, and triggered drug release profiles in a variety of tissues.
文摘Subcellular organelle-specific nanoparticles for simultaneous tumor targeting, imaging, and drug delivery are of enormous interest in cancer therapy. Herein, we report a selective mitochondria-targeting probe 1, which was synthesized by incorporating a triphenyl phosphine with a cyanostilbene and a long alkyl chain moiety. Probe 1 was found to display fluorescence via aggregation-induced emission （AIE）. The low molecular-weight cyanostilbene-based probe 1, with and without an anticancer drug, formed a narrow homogeneous nanorod with ca. 110 nm of length or nanopartides with ca. 20 nm diameter in aqueous media. The self-assembled cyanostilbene nanoparticles （N1） selectively accumulated in the mitochondria of cancer cells and emitted fluorescence. N1 was also able to deliver an anticancer drug, doxorubicin （DOX）, to the mitochondria with high efficiency. More importantl~ N1 exhibited highly selective cytotoxicity for cancer cells over normal cells. The great potential applications of this self-assembled nanoparticle to biological systems result from its ability to aggregate in the mitochondria. This aggregation led to a significant increase in the generation of intraceUular reactive oxygen species and to a decrease in the mitochondrial membrane potential in cancer cells. Furthermore, tumor tissue uptake experiments in mice proposed that the self-assembled N1 had the ability to internalize and deliver the anticancer drug into tumor tissues effectively. Moreover, both N1 and Nl-encapsulated doxorubicin （N1-DOX） effectively suppressed tumor growth in a xenograft model in vivo. Taken together, our findings indicate that applications of N1 as a mitochondrial targeting probe, drug delivery platform, and chemotherapeutic agent provide a unique strategy for potential image-guided therapy as well as a site-specific delivery system to cancer cells.
文摘Recently, covalent-organic polymers （COPs）, which covalently cross-link different types of organic molecules to form organic network structures, have received significant attention in various fields. However, the design of COPs that allows them to act as therapeutic agents remains to be explored. In the present study, a new class of COPs was fabricated by cross-linking the photosensitizer meso-tetra（p-hydroxyphenyl） porphine （THPP） to a chemotherapeutic pro-drug, cis-platinum （IV）; the latter also acts as a reduction-responsive linker. After further conjugation with polyethylene glycol （PEG） in this one-pot reaction, we obtained THPP-Pt-PEG COPs, which can be stored in a lyophilized form and occur as stable nanoparticles in aqueous solution. The THPP-Pt-PEG COPs are effective in killing cancer cells through photodynamic treatment, and exhibited reduction-responsive degradation/drug release behaviors. Upon intravenous injection, the COPs, with a long blood circulation time, showed efficient tumor accumulation. Interestingly, we revealed that after injection of THPP-Pt-PEG COPs, tumors on mice exhibited greatly improved vascular perfusion and largely relieved tumor hypoxia, which favored subsequent photodynamic treatment. Hence, the combined chemo-photodynamic therapy of the COPs offers a remarkably improved therapeutic outcome compared to that with mono-therapies. This work presents a COP-based nanomedicine with high drug loading, lyophilizable formulation, prolonged blood half-life, efficient tumor passive homing, inherent biodegradability, and multiple therapeutic functions to achieve enhanced cancer combination therapy, with promise for clinical translation.
