Nanoparticles containing insoluble drug for cancer therapy

Nanoparticle drug formulations have been extensively researched and developed in the field of drug delivery as a means to efficiently deliver insoluble drugs to tumor cells. By mechanisms of the enhanced permeability and retention effect, nanoparticle drug formulations are capable of greatly enhancing the safety, pharmacokinetic profiles and bioavailability of the administered treatment. Here, the progress of various nanoparticle formulations in both research and clinical applications is detailed with a focus on the development of drug/gene delivery systems. Specifically, the unique advantages and disadvanges of polymeric nanoparticles, liposomes, solid lipid nanoparticles, nanocrystals and lipid-coated nanoparticles for targeted drug delivery will be investigated in detail

AdaCompress: Adaptive Compression for Online Computer Vision Services

With the growth of computer vision based applications and services, an explosive amount of images have been uploaded to cloud servers which host such computer vision algorithms, usually in the form of deep learning models. JPEG has been used as the {\em de facto} compression and encapsulation method before one uploads the images, due to its wide adaptation. However, standard JPEG configuration does not always perform well for compressing images that are to be processed by a deep learning model, e.g., the standard quality level of JPEG leads to 50\% of size overhead (compared with the best quality level selection) on ImageNet under the same inference accuracy in popular computer vision models including InceptionNet, ResNet, etc. Knowing this, designing a better JPEG configuration for online computer vision services is still extremely challenging: 1) Cloud-based computer vision models are usually a black box to end-users; thus it is difficult to design JPEG configuration without knowing their model structures. 2) JPEG configuration has to change when different users use it. In this paper, we propose a reinforcement learning based JPEG configuration framework. In particular, we design an agent that adaptively chooses the compression level according to the input image's features and backend deep learning models. Then we train the agent in a reinforcement learning way to adapt it for different deep learning cloud services that act as the {\em interactive training environment} and feeding a reward with comprehensive consideration of accuracy and data size. In our real-world evaluation on Amazon Rekognition, Face++ and Baidu Vision, our approach can reduce the size of images by 1/2 -- 1/3 while the overall classification accuracy only decreases slightly.Comment: ACM Multimedi

PolyMetformin combines carrier and anticancer activities for in vivo siRNA delivery

Metformin, a widely implemented anti-diabetic drug, exhibits potent anticancer efficacies. Herein a polymeric construction of Metformin, PolyMetformin (PolyMet) is successfully synthesized through conjugation of linear polyethylenimine (PEI) with dicyandiamide. The delocalization of cationic charges in the biguanide groups of PolyMet reduces the toxicity of PEI both in vitro and in vivo. Furthermore, the polycationic properties of PolyMet permits capture of siRNA into a core-membrane structured lipid-polycation-hyaluronic acid (LPH) nanoparticle for systemic gene delivery. Advances herein permit LPH-PolyMet nanoparticles to facilitate VEGF siRNA delivery for VEGF knockdown in a human lung cancer xenograft, leading to enhanced tumour suppressive efficacy. Even in the absence of RNAi, LPH-PolyMet nanoparticles act similarly to Metformin and induce antitumour efficacy through activation of the AMPK and inhibition of the mTOR. In essence, PolyMet successfully combines the intrinsic anticancer efficacy of Metformin with the capacity to carry siRNA to enhance the therapeutic activity of an anticancer gene therapy

Unmodified drug used as a material to construct nanoparticles: delivery of cisplatin for enhanced anti-cancer therapy

The poor solubility of cisplatin (CDDP) often presents a major obstacle in the formulation of CDDP in nanoparticles (NPs) by traditional methods. We have developed a novel method for synthesizing CDDP NPs taking advantage of its poor solubility. By mixing two reverse microemulsions containing KCl and a highly soluble precursor of CDDP, cis-diaminedihydroplatinum (II), we have successfully formulated CDDP NPs with a controllable size (in the range of 12–75 nm) and high drug loading capacity (approximately 80 wt%). The formulation was done in two steps. The pure CDDP NPs were first stabilized for dispersion in an organic solvent by coating with 1, 2-dioleoyl-sn-glycero-3-phosphate (DOPA). Both x-ray photoelectron spectroscopy and 1H NMR data confirmed that the major ingredient of the DOPA-coated NPs was CDDP. After purification, additional lipids were added to stabilize the NPs for dispersion in an aqueous solution. The final NPs contain a lipid bilayer coating and are named Lipid-Pt-Cl (LPC) NPs, which showed significant antitumor activity both in vitro and in vivo. Thus, CDDP precipitate serves as the major material for assembling the novel NPs. This unique method of nanoparticle synthesis may be applicable in formulating other insoluble drugs

Incorporation of histone derived recombinant protein for enhanced disassembly of core-membrane structured liposomal nanoparticles for efficient siRNA delivery

A novel recombinant protein tetra-H2A (TH) derived from histone H2A has been developed to replace protamine as a conditionally reversible, nucleic acid condensing agent. The novel protein will address the insufficient release of nucleic acid therapeutics, which is captured by protamine for siRNA delivery. TH is composed of 4 tandem repeats of the histone H2A N-terminal sequence, intervened by the cathepsin D cleavage site. The repeating H2A sequence enhances the binding affinity to anionic nucleic acids, forming more stable condensates, as demonstrated by the binding affinity assay. The TH/siRNA condensates are formulated into a core-membrane structured liposomal nanoparticle (NP). The endosomes of cancer cells are rich in cathepsin D, allowing on-site degradation of TH and facilitating the intracellular release of siRNA. The NPs assembled with TH produced a higher silencing efficiency of target genes in vitro and in vivo than the NPs assembled with protamine as the nucleic acid condensing agent. The exploitation of TH in the NP formulation exhibited a biocompatibility profile similar to that of protamine, with minimal immunostimulating and systemic toxicity observed after repeated administration

Hypothesis Paper Effects of Intracellular Superoxide Removal at Acupoints with TAT-SOD on Obesity

TAT-SOD is a recombinant protein of superoxide dismutase fused with TAT peptide. By pure accident, we discovered that topical application of TAT-SOD to acupoints could result in acupuncture-like action. This study aimed to validate the accidental discovery by investigating the effect on simple obesity of the topical application of TAT-SOD to acupoints in comparison with acupuncture. 90 subjects were divided into 3 groups for 12-week treatments. Regular hospital acupuncture treatment was given to Acupuncture Group 3 times a week. TAT-SOD Group were instructed first to locate acupoints and apply 0.1 ml of 5000u SOD/ml TAT-SOD cream in an area of 1 cm 2 to each of the same set of acupoints, which they then conducted at home three times daily. Placebo Group applied the vehicle cream the same manner as TAT-SOD Group. Both TAT-SOD and acupuncture treatments decreased adiposity with overall clinical effective rates of 60.0% and 76.7%, respectively. The placebo group showed no improvement. The results validate that the enzymatic removal of the intracellular superoxide at acupoints could generate acupuncture-like effects, and indicate a possibility of the new method as a simple substitute to acupuncture and an insight of superoxide modulation along meridians for acupuncture mechanism. © 2011 Elsevier Inc. All rights reserved. Introduction Superoxide is one of the main reactive oxygen species (ROS) in the cell, which act as second messengers in the intracellular signaling pathways involved in activation of proinflammatory responses and mediate degradation of aggregan and collagen Although a variety of exogenous anti-oxidant enzymes are available to protect against oxidative stresses, the major problem in using these enzymes is that they can not be delivered into cells, thus resulting in their inability to detoxify intracellular RO

Nanoparticles with Precise Ratiometric Co-Loading and Co-Delivery of Gemcitabine Monophosphate and Cisplatin for Treatment of Bladder Cancer

Combination chemotherapy is a common practice in clinical management of malignancy. Synergistic therapeutic outcome is only achieved when tumor cells are exposed to cells in an optimal ratio. However, due to diverse physicochemical properties of drugs, no free drug cocktails or nanomaterials are capable of co-loading and co-delivering drugs at an optimal ratio. Herein, we develop a novel nano-platform with precise ratiometric co-loading and co-delivery of two hydrophilic drugs for synergistic anti-tumor effects. Based on previous work, we utilize a solvent displacement method to ratiometrically load dioleoyl phosphatidic acid (DOPA)-gemcitabine monophosphate and DOPA coated cisplatin-precipitate nanocores into the same PLGA NP. These cores are designed to have similar hydrophobic surface properties. GMP and cisplatin are engineered into PLGA NP at an optimal synergistic ratio (5:1, mol:mol) with over 70% encapsulation efficiency and were ratiometrically taken up by tumor cells in vitro and in vivo. These PLGA NP exhibit synergistic anti-cancer effects in a stroma-rich bladder tumor model. A single injection of dual drugs in PLGA NP can significantly inhibit tumor growth. This nanomaterial-system solves problems related to ratiometric co-loading and co-delivery of different hydrophilic moieties and provides possibilities for co-loading hydrophilic drugs with hydrophobic drugs for combination therapy

Turning a water and oil insoluble cisplatin derivative into a nanoparticle formulation for cancer therapy

The formulation of water insoluble organic compounds into nanoparticles has become a widely established method for enhancing the delivery and efficacy of cancer therapeutics. Therefore, a comparable approach when applied to water insoluble inorganic compounds should also promote similar advantages. Herein, we have successfully formulated insoluble iodinated cisplatin (CDDP-I) into a LPI NPs (lipid-coated iodinated CDDP nanoparticles). Two separate microemulsions were combined, each containing a precursor for the synthesis of CDDP-I. The resulting CDDP-I precipitate was then coated with an anionic lipid and dispersed in water with the help of an additional lipid. This method allows us to effectively encapsulate CDDP-I and was able to achieve a considerable drug loading of 82 wt%. Administered LPI NPs demonstrated high level accumulation in tumor tissues and exhibited an anti-cancer activity comparable to free CDDP in two melanoma xenograft models without inducing nephrotoxocity. The benefits offered through this delivery formulation are not unique to CDDP-I, as this versatile platform may be extended to the formulation of other inorganic compounds that are both water and oil insoluble into nanoparticles for superior anticancer efficacy