RESUMO
Since the launch of the Alliance for Nanotechnology in Cancer by the National Cancer Institute in late 2004, several similar initiatives have been promoted all over the globe with the intention of advancing the diagnosis, treatment and prevention of cancer in the wake of nanoscience and nanotechnology. All this has encouraged scientists with diverse backgrounds to team up with one another, learn from each other, and generate new knowledge at the interface between engineering, physics, chemistry and biomedical sciences. Importantly, this new knowledge has been wisely channeled towards the development of novel diagnostic, imaging and therapeutic nanosystems, many of which are currently at different stages of clinical development. This roadmap collects eight brief articles elaborating on the interaction of nanomedicines with human biology; the biomedical and clinical applications of nanomedicines; and the importance of patient stratification in the development of future nanomedicines. The first article reports on the role of geometry and mechanical properties in nanomedicine rational design; the second articulates on the interaction of nanomedicines with cells of the immune system; and the third deals with exploiting endogenous molecules, such as albumin, to carry therapeutic agents. The second group of articles highlights the successful application of nanomedicines in the treatment of cancer with the optimal delivery of nucleic acids, diabetes with the sustained and controlled release of insulin, stroke by using thrombolytic particles, and atherosclerosis with the development of targeted nanoparticles. Finally, the last contribution comments on how nanomedicine and theranostics could play a pivotal role in the development of personalized medicines. As this roadmap cannot cover the massive extent of development of nanomedicine over the past 15 years, only a few major achievements are highlighted as the field progressively matures from the initial hype to the consolidation phase.
RESUMO
Conjugated polymers have been increasingly studied for photothermal therapy (PTT) because of their merits including large absorption coefficient, facile tuning of exciton energy dissipation through nonradiative decay, and good therapeutic efficacy. The high photothermal conversion efficiency (PCE) is the key to realize efficient PTT. Herein, a donor-acceptor (D-A) structured porphyrin-containing conjugated polymer (PorCP) is reported for efficient PTT in vitro and in vivo. The D-A structure introduces intramolecular charge transfer along the backbone, resulting in redshifted Q band, broadened absorption, and increased extinction coefficient as compared to the state-of-art porphyrin-based photothermal reagent. Through nanoencapsulation, the dense packing of a large number of PorCP molecules in a single nanoparticle (NP) leads to favorable nonradiative decay, good photostability, and high extinction coefficient of 4.23 × 104 m-1 cm-1 at 800 nm based on porphyrin molar concentration and the highest PCE of 63.8% among conjugated polymer NPs. With the aid of coloaded fluorescent conjugated polymer, the cellular uptake and distribution of the PorCP in vitro can be clearly visualized, which also shows effective photothermal tumor ablation in vitro and in vivo. This research indicates a new design route of conjugated polymer-based photothermal therapeutic materials for potential personalized theranostic nanomedicine.
Assuntos
Fototerapia/métodos , Polímeros/química , Porfirinas/química , Animais , Linhagem Celular Tumoral , Células HeLa , Humanos , Hiperplasia/terapia , Hepatopatias/terapia , Nanopartículas Metálicas/química , Nanomedicina Teranóstica/métodos , Peixe-ZebraRESUMO
Nanocrystals (NCs) are widely used in optoelectronics, photocatalysis, and bioimaging. As the surface area to volume ratio increases with a decrease in the size of NCs, strategies to control the size of NCs are highly valuable for many applications. Given the importance of photoluminescent dyes, especially those with aggregation-induced emission, the transformation from an amorphous to a crystalline state can yield a drastic enhancement in their optical properties, which is of significance for biomedical applications. Till now, there is no general method available for the synthesis of small NCs with accurate control over the size and uniformity. Herein, a simple and general approach of ouzo nanocrystallization is presented for the synthesis of small (<100 nm) and highly uniform (polydispersity index~0.1) NCs with good control over the size. The process of nanoprecipitation is used to synthesize uniform nanoparticles (NPs) with different size, which is followed by solvent addition to form swollen NPs. Further, the amorphous core of swollen NPs is converted into NCs within polymer shell under Ouzo zone, which restricts NCs to grow above certain size. To demonstrate the general applicability of ouzo nanocrystallization, two different classes of luminescent materials are used as examples to fabricate small and highly uniform NCs.
RESUMO
Polymeric nanoparticles play important roles in the delivery of a multitude of therapeutic and imaging contrast agents. Although these nanomaterials have shown tremendous potential in disease diagnosis and therapy, there have been many reports on the failure of these nanoparticles in realizing their intended objectives due to an individual or a combination of factors, which have collectively challenged the merit of nanomedicine for disease theranostics. Herein, we investigate the interactions of polymeric nanoparticles with biological entities from molecular to organism levels. Specifically, the protein corona formation, in vitro endothelial uptake, and in vivo circulation time of these nanoparticles are systematically probed. We identify the crucial role of nanocarrier lipophilicity, zeta-potential, and size in controlling the interactions between nanoparticles and biological systems and propose a two-step framework in formulating a single nanoparticle system to regulate multiple biological effects. This study provides insight into the rational design and optimization of the performance of polymeric nanoparticles to advance their theranostic and nanomedicine applications.
Assuntos
Nanopartículas , Nanoestruturas , Coroa de Proteína , Nanomedicina , Polímeros , Nanomedicina TeranósticaRESUMO
Horseradish peroxidase (HRP) and fluorogen-dextran conjugate are tracers extensively used for injection-based lineage tracing. However, HRP is sensitive to proteolytic digestion, whereas the high-molecular-weight dextran may have antigenicity. Small molecular tracers can overcome these problems, but they usually diffuse from labeled cells, causing inaccurate information. Herein, we developed a small-molecular-weight fluorogen with aggregation-induced emission (AIEgen) for embryonic cell tracing with strong signals against tracer dilution caused by cell division. Once injected into the ancestor cells, the AIEgen can be entrapped in the cells without leakage because of the two hydrophilic and neutral arms. Consequently, it can specifically trace the progenies of the treated ancestor cells. More importantly, the operating concentration of AIEgen can be much higher than that of fluorogens with aggregation-caused quenching, which provides bright signals in daughter cells during embryonic cell tracing, thus overcoming the problem of fast signal degradation typically encountered with the use of traditional cell tracers.
Assuntos
Diferenciação Celular/fisiologia , Animais , Divisão Celular/fisiologia , Dextranos/química , Peroxidase do Rábano Silvestre/metabolismo , Peixe-ZebraRESUMO
Activation of photosensitizers (PSs) in targeted lesion and minimization of reactive oxygen species (ROS) depletion by endogenous antioxidants constitute promising approaches to perform highly effective image-guided photodynamic therapy (PDT) with minimal non-specific phototoxicity. Traditional strategies to fabricate controllable PS platforms rely on molecular design, which requires specific modification of each PS before PDT. Therefore, construction of a general tumor-responsive PDT platform with minimum ROS loss from endogenous antioxidant, typically glutathione (GSH), is highly desirable. Herein, MOF-199, a Cu(II) carboxylate-based metal-organic framework (MOF), is selected to serve as an inert carrier to load PSs with prohibited photosensitization during delivery. After cellular uptake, Cu (II) in the MOFs effectively scavenges endogenous GSH, concomitantly induces decomposition of MOF-199 to release the encapsulated PSs, and recovers their ROS generation. In vitro and in vivo experiments demonstrate highly effective cancer cell ablation and anticancer PDT with diminished normal cell phototoxicity. This strategy is generally applicable to PSs with both aggregation-induced emission and aggregation-caused quenching to implement activatable and enhanced image-guided PDT.
Assuntos
Antineoplásicos/química , Estruturas Metalorgânicas/química , Nanoconjugados/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Células 3T3 , Animais , Antineoplásicos/administração & dosagem , Liberação Controlada de Fármacos , Glutationa/metabolismo , Células Hep G2 , Humanos , Camundongos , Fármacos Fotossensibilizantes/administração & dosagemRESUMO
Multiplexed cellular organelle imaging using single wavelength excitation is highly desirable for unravelling cellular functions but remains challenging. This requires the design of organelle specific fluorophores with distinct emission but similar absorption. Herein, we present two unique aggregation-induced emission (AIE) probes to track mitochondria and lysosomes simultaneously with emission colors that can be distinguished from that of the nucleus stain Hoechst 33342 upon single wavelength excitation. Compared to conventional organelle stains, the two AIE probes have larger Stokes shifts and higher photostability, which endow them with the capability to monitor bioprocesses, such as mitophagy with strong and sustained fluorescent signals. Moreover, both probes can also stain intracellular organelles in zebrafish larvae with good cell-penetrating capabilities, showing their great potential to monitor bioprocesses in vivo.
RESUMO
Photodynamic therapy (PDT) employs accumulation of photosensitizers (PSs) in malignant tumor tissue followed by the light-induced generation of cytotoxic reactive oxygen species to kill the tumor cells. The success of PDT depends on optimal PS dosage that is matched with the ideal power of light. This in turn depends on PS accumulation in target tissue and light administration time and period. As theranostic nanomedicine is driven by multifunctional therapeutics that aim to achieve targeted tissue delivery and image-guided therapy, fluorescent PS nanoparticle (NP) accumulation in target tissues can be ascertained through fluorescence imaging to optimize the light dose and administration parameters. In this regard, zebrafish larvae provide a unique transparent in vivo platform to monitor fluorescent PS bio-distribution and their therapeutic efficiency. Using fluorescent PS NPs with unique aggregation-induced emission characteristics, we demonstrate for the first time the real-time visualization of polymeric NP accumulation in tumor tissue and, more importantly, the best time to conduct PDT using transgenic zebrafish larvae with inducible liver hyperplasia as an example.
RESUMO
Aggregation-caused quenching (ACQ) is a general phenomenon that is faced by traditional fluorescent polymers. Aggregation-induced emission (AIE) is exactly opposite to ACQ. AIE molecules are almost nonemissive in their molecularly dissolved state, but they can be induced to show high fluorescence in the aggregated or solid state. Incorporation of AIE phenomenon into polymer design has yielded various polymers with AIE characteristics. In this review, the recent progress of AIE polymers for biological applications is summarized.
Assuntos
Polímeros/química , Fluorescência , Polimerização , Polímeros/síntese química , Polímeros/farmacologia , SolubilidadeRESUMO
Conjugated polymer nanoparticles (CP NPs) are emerging candidates of "all-in-one" theranostic nanoplatforms with dual photoacoustic imaging (PA) and photothermal therapy (PTT) functions. So far, very limited molecular design guidelines have been developed for achieving CPs with highly efficient PA and PTT performance. Herein, by designing CP1, CP2, and CP3 using different electron acceptors (A) and a planar electron donor (D), we demonstrate how the D-A strength affects their absorption, emission, extinction coefficient, and ultimately PA and PTT performance. The resultant CP NPs have strong PA signals with high photothermal conversion efficiencies and excellent biocompatibility in vitro and in vivo. The CP3 NPs show a high PA signal to background ratio of 47 in U87 tumor-bearing mice, which is superior to other reported PA/PTT theranostic agents. A very small IC50 value of 0.88 µg/mL (CP3 NPs) was obtained for U87 glioma cell ablation under laser irradiation (808 nm, 0.8 W/cm2, 5 min). This study shows that CP NP based theranostic platforms are promising for future personalized nanomedicine.
Assuntos
Antineoplásicos/farmacologia , Materiais Biocompatíveis/farmacologia , Nanopartículas/química , Técnicas Fotoacústicas , Fototerapia , Polímeros/farmacologia , Nanomedicina Teranóstica , Animais , Antineoplásicos/química , Materiais Biocompatíveis/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Polímeros/químicaRESUMO
A two-channel responsive and AIE-active fluorescent probe was developed to selectively detect superoxide anions in living cells, which can be used to track the endogenous superoxide anion level when cells undergo apoptosis and inflammation.