Platinum-based anticancer drugs occupy a crucial role in the treatment of various malignant tumours. However, the efficacy and applicability of platinum drugs are heavily restricted by severe ...systemic toxicities and drug resistance. Different drug targeting and delivery (DTD) strategies have been developed to prevent the shortcomings of platinum-based chemotherapy. These approaches can be roughly categorized into two groups; namely, active and passive tactics. Active DTD is realized through specific molecular interactions between the drugs and cell or tissue elements, while passive DTD is achieved by exploiting the enhanced permeability and retention effect in tumour tissues. The principal methods for active DTD include conjugation of platinum drugs with selective targeting moieties or encapsulation of platinum drugs in host molecules. Bioactive substances such as hormones, carbohydrates, bisphosphonates, peptides and proteins are commonly used in active DTD. Passive DTD generally involves the fabrication of functionalized polymers or nanoparticles and the subsequent conjugation of platinum drugs with such entities. Polymeric micelles, liposomes, nanotubes and nanoparticles are frequently used in passive DTD. In some cases, both active and passive mechanisms are involved in one DTD system. This review concentrates on various targeting and delivery techniques for improving the efficacy and reducing the side effects of platinum-based anticancer drugs. The content covers most of the related literatures published since 2006. These innovative tactics represent current state-of-the-art developments in platinum-based anticancer drugs.
Platinum-based anticancer drugs are the mainstay of chemotherapy regimens in clinic. Nevertheless, the efficacy of platinum drugs is badly affected by serious systemic toxicities and drug resistance, ...and the pharmacokinetics of most platinum drugs is largely unknown. In recent years, a keen interest in functionalizing platinum complexes with bioactive molecules, targeting groups, photosensitizers, fluorophores, or nanomaterials has been sparked among chemical and biomedical researchers. The motivation for functionalization comes from some of the following demands: to improve the tumor selectivity or minimize the systemic toxicity of the drugs, to enhance the cellular accumulation of the drugs, to overcome the tumor resistance to the drugs, to visualize the drug molecules in vitro or in vivo, to achieve a synergistic anticancer effect between different therapeutic modalities, or to add extra functionality to the drugs. In this Account, we present different strategies being used for functionalizing platinum complexes, including conjugation with bisphosphonates, peptides, receptor-specific ligands, polymers, nanoparticles, magnetic resonance imaging contrast agents, metal chelators, or photosensitizers. Among them, bisphosphonates, peptides, and receptor-specific ligands are used for actively targeted drug delivery, polymers and nanoparticles are for passively targeted drug delivery, magnetic resonance imaging contrast agents are for theranostic purposes, metal chelators are for the treatment or prevention of Alzheimer's disease (AD), and photosensitizers are for photodynamic therapy of cancers. The rationales behind these designs are explained and justified at the molecular or cellular level, associating with the requirements for diagnosis, therapy, and visualization of biological processes. To illustrate the wide range of opportunities and challenges that are emerging in this realm, representative examples of targeted drug delivery systems, anticancer conjugates, anticancer theranostic agents, and anti-AD compounds relevant to functionalized platinum complexes are provided. All the examples exhibit new potential of platinum complexes for future applications in biomedical areas. The emphases of this Account are placed on the functionalization for targeted drug delivery and theranostic agents. In the end, a general assessment of various strategies has been made according to their major shortcomings and defects. The original information in this Account comes entirely from literature appearing since 2010.
Platinum-based anticancer chemotherapy constitutes a cornerstone for the treatment of various solid tumors. However, existing platinum drugs like cisplatin encounter many obstacles such as drug ...resistance and systemic toxicity in clinical applications. Extensive attempts have been made to minimize the side effects of platinum drugs. This review concentrates on the major development of novel platinum complexes in the last five years, and highlights the complexes with DNA damage mode fundamentally different from that of cisplatin. Diverse platinum complexes are discussed in the text, including analogues of cisplatin or oxaliplatin, monofunctional platinum(II) complexes, polynuclear platinum(II) complexes, trans-platinum(II) complexes, and platinum(IV) complexes. All of these complexes display impressive antitumor activity and some of them show remarkable potentiality to circumvent the resistance to cisplatin. On the basis of these new facts, it can be concluded that structural modifications could substantially modulate the DNA binding mode and DNA damage process, and as a result largely improve the antitumor efficacy of platinum complexes.
Semiconductor mixed-halide perovskites featured with a tunable energy bandgap are ideal candidates for light absorbers in tandem solar cells as well as fluorescent materials in light-emitting diodes ...and nanoscale lasers. These device advancements are currently hindered by the light-induced phase segregation effect, whereby ion migration would yield smaller-bandgap domains with red-shifted photoluminescence. Here we show that upon laser excitation all-inorganic mixed-halide nanocrystals unexpectedly exhibit a blue shift in the photoluminescence peak that can revert back in the dark, thus depicting the processes of ion migration out of and back to the originally excited nanocrystals. Interestingly, this reversible photoluminescence shift can also be induced by electrical biasing of mixed-halide nanocrystals without the injection of charge carriers. The above findings suggest that it is the local electric field that breaks the ionic bonds in mixed-halide nanocrystals, which could be a universal origin for light-induced phase segregation observed in other mixed-halide perovskite materials.
Abstract
Artificial photosynthesis, light-driving CO
2
conversion into hydrocarbon fuels, is a promising strategy to synchronously overcome global warming and energy-supply issues. The quaternary ...AgInP
2
S
6
atomic layer with the thickness of ~ 0.70 nm were successfully synthesized through facile ultrasonic exfoliation of the corresponding bulk crystal. The sulfur defect engineering on this atomic layer through a H
2
O
2
etching treatment can excitingly change the CO
2
photoreduction reaction pathway to steer dominant generation of ethene with the yield-based selectivity reaching ~73% and the electron-based selectivity as high as ~89%. Both DFT calculation and
in-situ
FTIR spectra demonstrate that as the introduction of S vacancies in AgInP
2
S
6
causes the charge accumulation on the Ag atoms near the S vacancies, the exposed Ag sites can thus effectively capture the forming *CO molecules. It makes the catalyst surface enrich with key reaction intermediates to lower the C-C binding coupling barrier, which facilitates the production of ethene.
Uniform plasmonic Pd@Au core–shell bimetallic nanoplates are synthesized by seeded growth strategy. Surface modified with SH‐PEG makes it good biocompatibility, prolonged blood circulation, and ...relatively high tumor accumulation. Enhanced tumor contrast effects can be obtained for in vivo photoacoustic/CT imaging after intravenous injection of Pd@Au‐PEG. Moreover, efficient photothermal tumor ablation is achieved, guided by the imaging techniques. This work promises further exploration of the superiority of 2D nanostructures for in vivo biomedical applications.
A new generation of photothermal theranostic agents is developed based on PEGylated WS2 nanosheets. Bimodal in vivo CT/photoacoustic imaging reveals strong tumor contrast after either intratumoral or ...intravenous injection of WS2‐PEG. In vivo photothermal treatment is then conducted in a mouse tumor model, achieving excellent therapeutic efficacy with complete ablation of tumors. This work promises further exploration of transition‐metal dichalcogenides for biomedical applications, such as cancer imaging and therapy.
Breast cancer (BC) is one of the most common malignancies in women and often accompanied by inflammatory processes. Cyclooxygenase‐2 (COX‐2) plays a vital role in the progression of BC, correlating ...with the expression of programmed death‐ligand 1 (PD‐L1). Overexpression of PD‐L1 contributes to the immune escape of cancer cells, and its blockade would stimulate anticancer immunity. Two multispecific platinum(IV) complexes DNP and NP were prepared using non‐steroidal antiinflammatory drug naproxen (NPX) as axial ligand(s) to inhibit the BC cells. DNP exhibited high cytotoxicity and antiinflammatory properties superior over NP, cisplatin and NPX; moreover, it displayed potent antitumor activity and almost no general toxicity in mice bearing triple‐negative breast cancer (TNBC). Mechanistic studies revealed that DNP could downregulate the expression of COX‐2 and PD‐L1 in vitro and vivo, inhibit the secretion of prostaglandin, reduce the expression of BC‐associated protein BRD4 and phosphorylation of extracellular signal‐regulated kinases 1/2 (Erk1/2), and block the oncogene c‐Myc in BC cells. These findings demonstrate that DNP is capable of intervening in inflammatory, immune, and metastatic processes of BC, thus presenting a new mechanism of action for anticancer platinum(IV) complexes. The multispecificity offers a special superiority for DNP to treat TNBC by combining chemotherapy and immunotherapy in one molecule.
A platinum(IV) complex (DNP) modified by the non‐steroidal antiinflammatory drug naproxen downregulated the expression of cyclooxygenase‐2 (COX‐2) and programmed death‐ligand 1 (PD‐L1) in vitro and vivo, retarded the metastasis of breast cancer cells, and showed potent antitumor activity in cancer‐bearing mice. Suppression on inflammatory cytokines and immune checkpoint is the unique character of DNP as a drug candidate.
Recently, near‐infrared (NIR) absorbing conjugated polymeric nanoparticles have received significant attention in photothermal therapy of cancer. Herein, polypyrrole (PPy), a NIR‐absorbing conjugate ...polymer, is used to coat ultra‐small iron oxide nanoparticles (IONPs), obtaining multifunctional IONP@PPy nanocomposite which is further modified by the biocompatible polyethylene glycol (PEG) through a layer‐by‐layer method to acquire high stability in physiological solutions. Utilizing the optical and magnetic properties of the yielded IONP@PPy‐PEG nanoparticles, in vivo magnetic resonance (MR) and photoacoustic imaging of tumor‐bearing mice are conducted, revealing strong tumor uptake of those nanoparticles after intravenous injection. In vivo photothermal therapy is then designed and carried out, achieving excellent tumor ablation therapeutic effect in mice experiments. These results promise the use of multifunctional NIR‐absorbing organic‐inorganic hybrid nanomaterials, such as IONP@PPy‐PEG presented here, for potential applications in cancer theranostics.
A novel type of multifunctional theranostic nanoparticles is developed by encapsulating ultra‐small iron oxide nanoparticles (IONPs) with polypyrrole (PPy), on top of which polyethylene glycol (PEG) is coated. The obtained IONP@PPy‐PEG nanoparticles with strong superparamagnetism and high near‐infrared absorbance enable in vivo dual‐modal magnetic resonance and photoacoustic imaging‐guided photothermal therapy, achieving excellent cancer ablation effect in animal experiments.
Due to the complex core-shell structure and variety of surface functional groups, the photoluminescence (PL) mechanism of carbon dots (CDs) remain unclear. o-Phenylenediamine (oPD), as one of the ...most common precursors for preparing red emissive CDs, has been extensively studied. Interestingly, most of the red emission CDs based on oPD have similar PL emission characteristics. Herein, we prepared six different oPD-based CDs and found that they had almost the same PL emission and absorption spectra after purification. Structural and spectral characterization indicated that they had similar carbon core structures but different surface polymer shells. Furthermore, single-molecule PL spectroscopy confirmed that the multi-modal emission of those CDs originated from the transitions of different vibrational energy levels of the same PL center in the carbon core. In addition, the phenomenon of "spectral splitting" of single-particle CDs was observed at low temperature, which confirmed these oPD-based CDs were unique materials with properties of both organic molecules and quantum dots. Finally, theoretical calculations revealed their potential polymerization mode and carbon core structure. Moreover, we proposed the PL mechanism of red-emitting CDs based on oPD precursors; that is, the carbon core regulates the PL emission, and the polymer shell regulates the PL intensity. Our work resolves the controversy on the PL mechanism of oPD-based red CDs. These findings provide a general guide for the mechanism exploration and structural analysis of other types of CDs.
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