Nano drug delivery systems for antisense oligonucleotides (ASO) therapeutics.

Cancer, infectious diseases, and metabolic and hereditary genetic disorders are a global health burden affecting millions of people, with contemporary treatments offering limited relief. Antisense technology treats diseases by targeting their causal agents using its ability to alter or inhibit endogenous or malfunctioning genes. Nine antisense oligonucleotide (ASO) drugs that represent four different chemical classes have been approved for the treatment of rare diseases, including nusinersen, the first new oligonucleotide-based drug.

Lipid nitroalkene nanoparticles for the focal treatment of ischemia reperfusion.

The treatment of microvascular obstruction (MVO) using ultrasound-targeted LNP cavitation (UTC) therapy mechanically relieves the physical obstruction in the microcirculation but does not specifically target the associated inflammatory milieu. Electrophilic fatty acid nitroalkene derivatives (nitro-fatty acids), that display pleiotropic anti-inflammatory signaling and transcriptional regulatory actions, offer strong therapeutic potential but lack a means of rapid targeted delivery. The objective of this study was to develop nitro-fatty acid-containing lipid nanoparticles (LNP) that retain the mechanical efficacy of standard LNP and can rapidly target delivery of a tissue-protective payload that reduces inflammation and improves vascular function following ischemia-reperfusion.

STAT3 decoy oligonucleotide-carrying microbubbles with pulsed ultrasound for enhanced therapeutic effect in head and neck tumors.

Signal transducer and activator of transcription-3 (STAT3) is an oncogenic transcription factor implicated in carcinogenesis, tumor progression, and drug resistance in head and neck squamous cell carcinoma (HNSCC). A decoy oligonucleotide targeting STAT3 offers a promising anti-tumor strategy, but achieving targeted tumor delivery of the decoy with systemic administration poses a significant challenge. We previously showed the potential for STAT3 decoy-loaded microbubbles, in conjunction with ultrasound targeted microbubble cavitation (UTMC), to decrease tumor growth in murine squamous cell carcinoma.

Smart Nanocarriers for the Delivery of Nucleic Acid-Based Therapeutics: A Comprehensive Review.

Nucleic acid-based therapies are promising therapeutics for the treatment of several systemic disorders, and they offer an exciting opportunity to address emerging biological challenges. The scope of nucleic acid-based therapeutics in the treatment of multiple disease states including cancers has been widened by recent progress in Ribonucleic acids (RNA) biology. However, cascades of systemic and intracellular barriers, including rapid degradation, renal clearance, and poor cellular uptake, hinder the clinical effectiveness of nucleic acid-based therapies.

Multi-responsive albumin-lonidamine conjugated hybridized gold nanoparticle as a combined photothermal-chemotherapy for synergistic tumor ablation.

Herein, we developed a multifunctional nanoplatform based on the nanoassembly of gold nanoparticles (GNP) conjugated with lonidamine (LND) and aptamer AS1411 (AS-LAGN) as an effective cancer treatment. Conjugating AS1411 aptamer on the surface of the nanoparticle significantly improved particle accumulation in cancer cells via specific affinity toward the nucleolin receptors. In vitro study clearly revealed that laser irradiation-based hyperthermia effect enhanced the chemotherapeutic effects of LND.

Polypeptide Derivative of Metformin with the Combined Advantage of a Gene Carrier and Anticancer Activity.

Metformin (MET) is a common treatment for type II diabetes. Here, we demonstrate the anticancer activity of a polymeric metformin derivative. We successfully synthesized the polypeptide (poly-l-lysine [PLL]) derivative of metformin (LysMET) and demonstrated its capacity as an anticancer therapeutic and gene carrier.

In situ fabrication of mesoporous silica-coated silver-gold hollow nanoshell for remotely controllable chemo-photothermal therapy via phase-change molecule as gatekeepers.

This study reports a new strategy for in situ fabrication of plasmonic hollow silver-gold nanoshell (with resonance tuned to NIR region) encased in the hollow mesoporous silica as an efficient platform to efficiently and precisely regulate the release of 5-fluorouracil (anticancer drug) for prostate cancer therapy and photothermal therapy. The mesopores were capped with thermosensitive phase-change material lauric acid, which allowed for remote, precise, and spatiotemporal control of drug release via external heating or photothermal heating of plasmonic silver-gold nanoshell via NIR laser irradiation. The system was nanometric, monodispersed, and showed negative surface charge.

PEGylated polyaminoacid-capped mesoporous silica nanoparticles for mitochondria-targeted delivery of celastrol in solid tumors.

The major goal of cancer chemotherapy is to maximize the therapeutic efficacy of anticancer drugs, while minimizing their associated side effects. Celastrol (CST), which is extracted from the traditional Chinese medicinal plant Tripterygium wilfordii, has been reported to exhibit significant anticancer effects in various in vitro and in vivo cancer models. Nanoparticulate drug delivery systems could be employed to preserve and enhance the pharmacological effects of CST in cancer cells.

Emerging potential of stimulus-responsive nanosized anticancer drug delivery systems for systemic applications.

The development of novel drug delivery systems based on well-defined polymer therapeutics has led to significant improvements in the treatment of multiple disorders. Advances in material chemistry, nanotechnology, and nanomedicine have revolutionized the practices of drug delivery. Stimulus-responsive material-based nanosized drug delivery systems have remarkable properties that allow them to circumvent biological barriers and achieve targeted intracellular drug delivery.

PEGylated thermosensitive lipid-coated hollow gold nanoshells for effective combinational chemo-photothermal therapy of pancreatic cancer.

Pancreatic cancer has extremely poor prognosis with an 85% mortality rate that results from aggressive and asymptomatic growth, high metastatic potential, and rapid development of resistance to already ineffective chemotherapy. In this study, plasmonic hollow gold nanoshells (GNS) coated with PEGylated thermosensitive lipids were prepared as an efficient platform to ratiometrically co-deliver two drugs, bortezomib and gemcitabine (GNS-L/GB), for combinational chemotherapy and photothermal therapy of pancreatic cancer. Bortezomib was loaded within the lipid bilayers, while gemcitabine was loaded into the hydrophilic interior of the porous GNS via an ammonium sulfate-driven pH gradient method.

Polyunsaturated fatty acid-based targeted nanotherapeutics to enhance the therapeutic efficacy of docetaxel.

Since breast cancer is one of the most lethal malignancies, targeted strategies are urgently needed. In this study, we report the enhanced therapeutic efficacy of docetaxel (DTX) when combined with polyunsaturated fatty acids (PUFA) for effective treatment of multi-resistant breast cancers. Folic acid (FA)-conjugated PUFA-based lipid nanoparticles (FA-PLN/DTX) was developed.

Facile construction of bioreducible crosslinked polypeptide micelles for enhanced cancer combination therapy.

Unlabelled: In this study, we developed pH and redox-responsive crosslinked polypeptide-based combination micelles for enhanced chemotherapeutic efficacy and minimized side effects. The stability and drug release properties of the polypeptide micelles were efficiency balanced by the corona-crosslinking of the triblock copolymer, poly(ethylene glycol)-b-poly(aspartic acid)-b-poly(tyrosine) (PEG-b-pAsp-b-pTyr) with coordinated redox and pH dual-sensitivity by introducing disulfide crosslinkages. Because of the crosslinking of the middle shell of the triblock polypeptide micelles, their robust structure was maintained in strong destabilization conditions and exhibited excellent stability.

Multiple polysaccharide-drug complex-loaded liposomes: A unique strategy in drug loading and cancer targeting.

In the present study, a unique strategy was developed to develop nanocarriers containing multiple therapeutics with controlled release characteristics. In this study, we demonstrated the synthesis of dextran sulfate-doxorubicin (DS-DOX) and alginate-cisplatin (AL-CIS) polymer-drug complexes to produce a transferrin ligand-conjugated liposome. The targeted nanoparticles (TL-DDAC) were nano-sized and spherical.

Smart chemistry-based nanosized drug delivery systems for systemic applications: A comprehensive review.

This review focuses on the smart chemistry that has been utilized in developing polymer-based drug delivery systems over the past 10years. We provide a comprehensive overview of the different functional moieties and reducible linkages exploited in these systems, and outline their design, synthesis, and application from a therapeutic efficacy viewpoint. Furthermore, we highlight the next generation nanomedicine strategies based on this novel chemistry.

Development of Bioactive PEGylated Nanostructured Platforms for Sequential Delivery of Doxorubicin and Imatinib to Overcome Drug Resistance in Metastatic Tumors.

Metastasis of cancers accounts for almost all cancer-related deaths. In this study, we report a PEGylated nanostructured platform for coadministration of doxorubicin (DOX) and imatinib (IMT) intended to effectively inhibit metastatic tumors. The DOX and IMT coloaded nanostructured system (DOX/IMT-N) is characterized by an excellent encapsulation potential for both drugs and shows sequential and sustained drug release in vitro.

Molecularly targeted co-delivery of a histone deacetylase inhibitor and paclitaxel by lipid-protein hybrid nanoparticles for synergistic combinational chemotherapy.

In this study, a transferrin-anchored albumin nanoplatform with PEGylated lipid bilayers (Tf-L-APVN) was developed for the targeted co-delivery of paclitaxel and vorinostat in solid tumors. Tf-L-APVN exhibited a sequential and controlled release profile of paclitaxel and vorinostat, with an accelerated release pattern at acidic pH. At cellular levels, Tf-L-APVN significantly enhanced the synergistic effects of paclitaxel and vorinostat on the proliferation of MCF-7, MDA-MB-231, and HepG2 cancer cells.

Layer-by-layer assembly of hierarchical nanoarchitectures to enhance the systemic performance of nanoparticle albumin-bound paclitaxel.

Although protein-bound paclitaxel (PTX, Abraxane) has been established as a standard PTX-based therapy against multiple cancers, its clinical success is limited by unfavorable pharmacokinetics, suboptimal biodistribution, and acute toxicities. In the present study, we aimed to apply the principles of a layer-by-layer (LbL) technique to improve the poor colloidal stability and pharmacokinetic pattern of nanoparticle albumin-bound paclitaxel (nab-PTX). LbL-based nab-PTX was successfully fabricated by the alternate deposition of polyarginine (pARG) and poly(ethylene glycol)-block-poly (L-aspartic acid) (PEG-b-PLD) onto an albumin conjugate.

PEGylated polypeptide lipid nanocapsules to enhance the anticancer efficacy of erlotinib in non-small cell lung cancer.

In this study, a core-shell type polypeptide-based lipid nanocapsule was developed to enhance anticancer efficacy of erlotinib in non-small cell lung cancers. Mean particle size of PEGylated polypeptide-lipid nanocapsules (PLN) for erlotinib (ERL) delivery was ∼200nm with an effective surface charge of -20mV. Protective PEGylated polypeptide layer acted as a molecular fence and effectively controlled the diffusion of erlotinib from the lipid nanocapsule core, whereas pH-responsiveness of poly(L-aspartic acid) accelerated the release of erlotinib in acidic conditions.

Engineering of cell microenvironment-responsive polypeptide nanovehicle co-encapsulating a synergistic combination of small molecules for effective chemotherapy in solid tumors.

Unlabelled: In this study, we report a facile method to construct a bioactive (poly(phenylalanine)-b-poly(l-histidine)-b-poly(ethylene glycol) polypeptide nanoconstruct to co-load doxorubicin (DOX) and quercetin (QUR) (DQ-NV). The smart pH-sensitive nanovehicle was fabricated with precisely tailored drug-to-carrier ratio that resulted in accelerated, sequential drug release. As a result of ratiometric loading, QUR could significantly enhance the cytotoxic potential of DOX, induced marked cell apoptosis; change cell cycle patterns, inhibit the migratory capacity of sensitive and resistant cancer cells.

Development of polymeric irinotecan nanoparticles using a novel lactone preservation strategy.

Irinotecan (IRT) is an important part of the first- and second-line regimen for metastatic colorectal and some other cancers. However, IRT suffers the constraints of pH-dependent conversion of active lactone form to inactive carboxylate form, burst release owing to its aqueous solubility, short half-life and dose-dependent side effects. In this study, we developed polymeric nanoparticles (NPs) that not only deliver IRT to tumor sites, but also overcome its drawbacks by preserving active lactone conformation, prolonging the plasma circulation time, and by providing sustained release.

Liquid crystalline nanoparticles encapsulating cisplatin and docetaxel combination for targeted therapy of breast cancer.

Cancer remains a leading cause of death. A combination of anticancer agents can effectively kill cancer through multiple pathways; however, improvements to their delivery are needed. Hence, docetaxel and cisplatin-loaded liquid crystalline nanoparticles with folic acid were prepared for effective and targeted anticancer therapy.

Engineering of caveolae-specific self-micellizing anticancer lipid nanoparticles to enhance the chemotherapeutic efficacy of oxaliplatin in colorectal cancer cells.

Unlabelled: Novel nanomaterials for the intracellular transport of therapeutic cargos have been actively sought to effectively breach cell-membrane barriers. In this study we developed novel self-micellizing anticancer lipid (SMAL)-based pro-apoptotic nanoparticles (NPs) that enhance the accumulation and chemotherapeutic efficacy of oxaliplatin (OL) in colorectal cancer cells (CRCs). We demonstrated that NPs with special affinity to caveolae could be designed and based on this specificity, NPs effectively differentiated between endothelial cells (tumor cells) and epithelial cells, without the need for a cell-specific targeting moiety.

Cationic drug-based self-assembled polyelectrolyte complex micelles: Physicochemical, pharmacokinetic, and anticancer activity analysis.

Nanofabrication of polymeric micelles through self-assembly of an ionic block copolymer and oppositely charged small molecules has recently emerged as a promising method of formulating delivery systems. The present study therefore aimed to investigate the interaction of cationic drugs doxorubicin (DOX) and mitoxantrone (MTX) with the anionic block polymer poly(ethylene oxide)-block-poly(acrylic acid) (PEO-b-PAA) and to study the influence of these interactions on the pharmacokinetic stability and antitumor potential of the formulated micelles in clinically relevant animal models. To this end, individual DOX and MTX-loaded polyelectrolyte complex micelles (PCM) were prepared, and their physicochemical properties and pH-responsive release profiles were studied.

PEGylated lipid bilayer-supported mesoporous silica nanoparticle composite for synergistic co-delivery of axitinib and celastrol in multi-targeted cancer therapy.

Unlabelled: Small-molecule drug combination therapies are an attractive approach to enhancing cancer chemotherapeutic responses. Therefore, this study aimed to investigate the potential of axitinib (AXT) and celastrol (CST) in targeting angiogenesis and mitochondrial-based apoptosis in cancer. Therefore, we prepared AXT/CST-loaded combination nanoparticles (ACML) with CST loaded in the mesoporous silica nanoparticles (MSN) and AXT in PEGylated lipidic bilayers.