Carrier-free nanodrugs for safe and effective cancer treatment

Clinical applications of many anti-cancer drugs are restricted due to their hydrophobic nature, requiring use of harmful organic solvents for administration, and poor selectivity and pharmacokinetics resulting in off-target toxicity and inefficient therapies. A wide variety of carrier-based nanoparticles have been developed to tackle these issues, but such strategies often fail to encapsulate drug efficiently and require significant amounts of inorganic and/or organic nanocarriers which may cause toxicity problems in the long term. Preparation of nano-formulations for the delivery of water insoluble drugs without using carriers is thus desired, requiring elegantly designed strategies for products with high quality, stability and performance. These strategies include simple self-assembly or involving chemical modifications via coupling drugs together or conjugating them with various functional molecules such as lipids, carbohydrates and photosensitizers. During nanodrugs synthesis, insertion of redox-responsive linkers and tumor targeting ligands endows them with additional characteristics like on-target delivery, and conjugation with immunotherapeutic reagents enhances immune response alongside therapeutic efficacy. This review aims to summarize the methods of making carrier-free nanodrugs from hydrophobic drug molecules, evaluating their performance, and discussing the advantages, challenges, and future development of these strategies

Robust Sequence Networked Submodular Maximization

In this paper, we study the \underline{R}obust \underline{o}ptimization for \underline{se}quence \underline{Net}worked \underline{s}ubmodular maximization (RoseNets) problem. We interweave the robust optimization with the sequence networked submodular maximization. The elements are connected by a directed acyclic graph and the objective function is not submodular on the elements but on the edges in the graph. Under such networked submodular scenario, the impact of removing an element from a sequence depends both on its position in the sequence and in the network. This makes the existing robust algorithms inapplicable. In this paper, we take the first step to study the RoseNets problem. We design a robust greedy algorithm, which is robust against the removal of an arbitrary subset of the selected elements. The approximation ratio of the algorithm depends both on the number of the removed elements and the network topology. We further conduct experiments on real applications of recommendation and link prediction. The experimental results demonstrate the effectiveness of the proposed algorithm.Comment: 12 pages, 14 figures, aaai2023 conference accepte

Label-Free Fluorescent Poly(amidoamine) Dendrimer for Traceable and Controlled Drug Delivery

Poly(amidoamine) dendrimer (PAMAM) is well-known for its high efficiency as a drug delivery vehicle. However, the intrinsic cytotoxicity and lack of a detectable signal to facilitate tracking have impeded its practical applications. Herein, we have developed a novel label-free fluorescent and biocompatible PAMAM derivative by simple surface modification of PAMAM using acetaldehyde. The modified PAMAM possessed a strong green fluorescence, which was generated by the C=N bonds of the resulting Schiff Bases via n-?∗ transition, while the intrinsic cytotoxicity of PAMAM was simultaneously ameliorated. Through further PEGylation, the fluorescent PAMAM demonstrated excellent intracellular tracking in human melanoma SKMEL28 cells. In addition, our PEGylated fluorescent PAMAM derivative achieved enhanced loading and delivery efficiency of the anticancer drug doxorubicin (DOX) compared to the original PAMAM. Importantly, the accelerated kinetics of DOX-encapsulated fluorescent PAMAM nanocomposites in an acidic environment facilitated intracellular drug release, which demonstrated comparable cytotoxicity to that of the free-form doxorubicin hydrochloride (DOX·HCl) against melanoma cells. Overall, our label free fluorescent PAMAM derivative offers a new opportunity of traceable and controlled delivery for DOX and other drugs of potential clinical importance

Synthesis of photo-excited Chlorin e6 conjugated silica nanoparticles for enhanced anti-bacterial efficiency to overcome methicillin-resistant Staphylococcus aureus

Multidrug resistant bacterial infection remains a significant public concern. In this report, photosensitizer Chlorin e6 doped silica was synthesized. This hybrid structure exhibits enhanced photostability and high antibacterial efficiency towards Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA). In summary, this work demonstrates an effective platform to improve the efficiency of antibiotics for better treatment of wound infections

Enhancement of gene therapy by exploring functional gene vectors based on chitosan modification.

Gene therapy is a broad term that encompasses any strategy to treat a disease by transferring an exogenous gene, gene segments, or oligonucleotides into patient’s cells to manipulate the defective genes or encoding the correct proteins. Gene therapy is becoming more efficient and has been successfully used in the treatment of genetic diseases such as cancers, infectious diseases, vascular diseases due to the rapid development of knowledge in elucidating the molecular basis of genetic diseases, as well as the availability of the complete sequence information of the human genome. However, it is difficult to obtain satisfactory efficiency by using naked nucleic acid without carrier/vectors since gene transfer in eukaryotic cells is a multiple-step process, in which naked nucleic acid can easily be digested. Therefore, the development of safe, efficient and specific delivery vectors for transporting appropriate genes to specific cells or tissues, where they can replace or regulate defective genes, is one of the key strategies in gene therapy. In my phD project, a serial of functional polymers, named chitosan supported imidazole Schiff-base (CISB), N-imidazolyl-O-carboxymethyl chitosan (IOCMCS), folic acid factionalized Schiff-base linked imidazole chitosan (FA-SLICS), have been designed and successfully developed as gene carriers based on the modification of chitosan. Additionally, a new strategy for promoting endoplasmic gene delivery and nucleus uptake has been proposed by developing pH-sensitive Schiff-base linked imidazole biodegradable polymers. This delivery system can efficiently load nucleic acids at a neutral pH, release imidazole-gene complexes from the polymer backbones at intracellular endosmal pH, transport nucleic acids into nucleus through multiple-stage intracellular gene delivery, and thus leads to a high cell transfection efficiency. These smart polymers display good biocompatibility, multiple-functions, and efficient gene delivery efficiency as gene carriers. Hence they have promising potential applications in future gene delivery and enhance the development of gene therapy.Thesis (Ph.D.) -- University of Adelaide, School of Chemical Engineering, 201

Rapid detection of rare-event cell by SUPER Dots based diagnostics nano-platform

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Controlling upconversion nanocrystals for emerging applications

Lanthanide-doped upconversion nanocrystals enable anti-Stokes emission with pump intensities several orders of magnitude lower than required by conventional nonlinear optical techniques. Their exceptional properties, namely large anti-Stokes shifts, sharp emission spectra and long excited-state lifetimes, have led to a diversity of applications. Here, we review upconversion nanocrystals from the perspective of fundamental concepts and examine the technical challenges in relation to emission colour tuning and luminescence enhancement. In particular, we highlight the advances in functionalization strategies that enable the broad utility of upconversion nanocrystals for multimodal imaging, cancer therapy, volumetric displays and photonics.13 page(s

Intracellular microenvironment-responsive label-free autofluorescent nanogels for traceable gene delivery

Gene therapy presents a unique opportunity for the treatment of genetic diseases, but the lack of multifunctional delivery systems has hindered its clinical applications. Here, a new delivery vector, autofluorescent polyethyleneimine (PEI) nanogels, for highly efficient and traceable gene delivery is developed. Different from commercial high-molecular-weight PEI, the cationic nanogels are noncytotoxic and able to be fragmented due to their unique intracellular microenvironment-responsive structures. The biodegradable nanogels can effectively load plasmid DNA (pDNA), and the self-assembled polyplexes can be cleaved after cellular uptake to improve gene transfection efficiency. Most importantly, the nanogels and the nanogel/pDNA polyplexes are autofluorescent. The fluorescence is stable in blood plasma and responsive to the intracellular microenvironment. The breakup of the nanogels or polyplexes leads to the loss of fluorescence, and thus the gene delivery and carrier biodegradation processes can be monitored. The reported multifunctional system demonstrates excellent biocompatibility, high transfection efficiency, responsive biodegradability, controlled gene release, label-free and simultaneous fluorescence tracking, which will provide a new platform for future scientific investigation and practical implications in gene therapy