Ph in cancer therapy

Researchers in various fields continue to discover improved ways of local delivery of drugs to specific locations and try to increase the efficiency of these methods. Extensive research has been done on smart nano-biomaterials for drug delivery systems (DDS) in different dimensions. With the advancement of biomedical nanotechnology, conventional smart DDS with stimuli- responsive capability has been developed. Smart nano-biomaterials can respond to environmental changes caused by endogenous or exogenous elements: endogenous factors such as environmental pH, temperature gradient, enzymes, oxidation, and reduction potential...

Colorectal carcinoma (CRC) has become one of the most prevalent malignant tumors and exploring a potential therapeutic strategy with diminished drug-associated adverse effects to combat CRC is urgent. Herein, we designed a pH-responsive polymer to efficiently encapsulate a stimulator of interferon genes (STING) agonist (5,6- dimethylxanthenone-4-acetic acid, termed ASA404) and a common clinically used chemotherapeutic agent (1-hexylcarbamoyl-5-fluorouracil, termed HCFU). Investigations in vitro demonstrated that polymer encapsulation endowed the system with a pH-dependent disassembly behavior (pHt 6...

In the last ten years, the field of nanomedicine has experienced significant progress in creating novel drug delivery systems (DDSs). An effective strategy involves employing DNA nanoparticles (NPs) as carriers to encapsulate drugs, genes, or proteins, facilitating regulated drug release. This abstract examines the utilization of DNA NPs and their potential applications in strategies for controlled drug release. Researchers have utilized the distinctive characteristics of DNA molecules, including their ability to self-assemble and their compatibility with living organisms, to create NPs specifically for the purpose of delivering drugs...

Triple-negative breast cancer (TNBC) is a highly invasive and metastatic subtype of breast cancer that often recurs after surgery. Herein, we developed a cyclodextrin-based tumor-targeted nano delivery system that incorporated the photosensitizer chlorin e6 (Ce6) and the chemotherapeutic agent lonidamine (LND) to form the R6RGD-CMβCD-se-se-Ce6/LND nanoparticles (RCC/LND NPS). This nanosystem could target cancer cells, avoid lysosomal degradation and further localize within the mitochondria. The RCC/LND NPS had pH and redox-responsive to control the release of Ce6 and LND...

Targeting enzymes involved in lipid metabolism is increasingly recognized as a promising anticancer strategy. Efficient inhibition of diacylglycerol O-transferase 1 (DGAT1) can block fatty acid (FA) storage. This, in turn, triggers an increase in free polyunsaturated FA concentration, leading to peroxidation and ferroptosis. In this study, we report the development of a pH-sensitive peptide (pHLIP)-drug conjugate designed to selectively deliver DGAT1 inhibitors to cancer cells nested within the acidic microenvironment of tumors...

Effective antitumor immunotherapy depends on evoking a cascade of cancer-immune cycles with lymph nodes (LNs) as the initial sites for activating antitumor immunity, making drug administration through the lymphatic system highly attractive. Here, we describe a nanomedicine with dual responsiveness to pH and enzyme for a programmed activation of antitumor immune through the lymphatic system. The proposed nanomedicine can release the STING agonist diABZI-C2-NH2 in the LNs' acidic environment to activate dendritic cells (DCs) and T cells...

Immunotherapy is an emerging approach for the treatment of solid tumors. Although chemotherapy is generally considered immunosuppressive, specific chemotherapeutic agents can induce tumor immunity. In this study, we developed a targeted, acid-sensitive peptide nanoparticle (DT/Pep1) to deliver doxorubicin (DOX) and triptolide (TPL) to breast cancer cells via the enhanced permeability and retention (EPR) effect and the breast cancer-targeting effect of peptide D8. Compared with administration of the free drugs, treatment with the DT/Pep1 system increased the accumulation of DOX and TPL at the tumor site and achieved deeper penetration into the tumor tissue...

Hepatocellular carcinoma (HCC) exhibits high mortality rates in the advanced stage (>90 %). Sorafenib (SORA) is a targeted therapy approved for the treatment of advanced HCC; however, the reported response rate to such a therapeutic is suboptimal (<3%). Piperine (PIP) is an alkaloid demonstrated to exert a direct tumoricidal activity in HCC and improve the pharmacokinetic profiles of anticancer drugs including SORA. In this study, we developed a strategy to improve efficacy outcomes in HCC using PIP as an add-on treatment to support the first-line therapy SORA using biodegradable Poly (D, L-Lactide-co-glycolide, PLGA) nanoparticles (NPs)...

The Russell mechanism, proposed by Russell, is a cyclic mechanism for the formation of linear tetroxide intermediates, which can spontaneously produce cytotoxic singlet oxygen (1O2) independent of oxygen, suggesting its anticancer potential. Compared with other mainstream anticancer strategies, the Russell mechanism employed for killing cancer cells does not require external energy input, harsh pH condition, and sufficient oxygen. However, up till now, the applications of Russell mechanism in antitumor therapy have been relatively rare, and there is almost no summary of the Russell mechanism in the cancer therapy field...

To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19 F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H6 ) to form H6 -PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs...

The development of chemoresistance is a major obstacle in post-surgical adjuvant therapy of cancer, leading to cancer cell survival, recurrence, and metastasis. This study reports a 3D-printed plasmonic implant developed for the post-surgical adjuvant therapy of cisplatin-resistant cancer cells to prevent relapse. The implant was printed using optimized biomaterial ink containing biodegradable polymers [poly(L-lactide) and hydroxypropyl methylcellulose] blended suitably with laser-responsive graphene and chemo drug (Cisplatin)...

BACKGROUND: The alpha emitter astatine-211 (211 At) is garnering attention as a novel targeted alpha therapy for patients with refractory thyroid cancer resistant to conventional therapy using beta emitter radioiodine (131 I). Herein, we aimed to establish a robust method for the manufacturing and quality control of [211 At]NaAt solution for intravenous administration under the good manufacturing practice guidelines for investigational products to conduct an investigator-initiated clinical trial...

Despite decades of laboratory and clinical trials, breast cancer remains the main cause of cancer-related disease burden in women. Considering the metabolism destruction effect of metformin (Met) and cancer cell starvation induced by glucose oxidase (GOx), after their efficient delivery to tumor sites, GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ . Herein, a pH-responsive epigallocatechin gallate (EGCG)-conjugated low-molecular-weight chitosan (LC-EGCG, LE) nanoparticle (Met-GOx/Fe@LE NPs) was constructed...

Cancer-related pain is considered one of the most prevalent symptoms for those affected by cancer, significantly influencing quality of life and treatment outcomes. Morphine is currently employed for analgesic treatment in this case, however, chronic use of this opioid is limited by the development of analgesic tolerance and adverse effects, such as digestive and neurological disorders. Alternative therapies, such as ion channel blockade, are explored. The toxin Phα1β has demonstrated efficacy in blocking calcium channels, making it a potential candidate for alleviating cancer-related pain...

The combination of peptides and nanoparticles in cancer therapy has shown synergistic results. Nanoparticle functionalization with peptides can increase their targeting ability towards tumor cells. In some cases, the peptides can develop self-assembled nanoparticles, in combination with drugs, for targeted cancer therapy. The peptides can be loaded into nanoparticles and can be delivered by other drugs for synergistic cancer removal. Multifunctional types of peptide-based nanoparticles, including pH- and redox-sensitive classes, have been introduced in cancer therapy...

Near-Infrared-II (NIR-II) spans wavelengths between 1,000 to 1,700 nanometers, featuring deep tissue penetration and reduced tissue scattering and absorption characteristics, providing robust support for cancer treatment and tumor imaging research. This review explores the utilization of activatable NIR-II photodiagnosis and phototherapy based on tumor microenvironments (e.g., reactive oxygen species, pH, glutathione, hypoxia) and external stimuli (e.g., laser, ultrasound, photothermal) for precise tumor treatment and imaging...

The management of CSPH in patients undergoing systemic treatment for HCC has emerged as a critical concern due to the absence of reliable diagnostic criteria and uncertainties surrounding therapeutic approaches. This review aims to underscore the primary pathophysiological aspects linking HCC and PH, while also addressing the current and emerging clinical strategies for the management of portal hypertension. A review of studies from January 2003 to June 2023 was conducted using the PubMed database and employing MeSH terms, such as "hepatocellular carcinoma", "immune checkpoint inhibitors", "systemic therapy", "portal hypertension", "variceal bleeding" and "tyrosine kinase inhibitors"...

BACKGROUND: Oral cancer is the most common malignant tumor of the head and neck, and 90% of cases are oral squamous cell carcinoma (OSCC). Chemotherapy is an important component of comprehensive treatment for OSCC. However, the clinical treatment effect of chemotherapy drugs, such as doxorubicin (DOX), is limited due to the lack of tumor targeting and rapid clearance by the immune system. Thus, based on the tumor-targeting and immune evasion abilities of macrophages, macrophage membrane-encapsulated poly(methyl vinyl ether alt maleic anhydride)-phenylboronic acid-doxorubicin nanoparticles (MM@PMVEMA-PBA-DOX NPs), briefly as MM@DOX NPs, were designed to target OSCC...

A promising therapeutic strategy in cancer treatment merges photodynamic therapy (PDT) induced apoptosis with ferroptosis, a form of programmed cell death governed by iron-dependent lipid peroxidation. Given the pivotal role of mitochondria in ferroptosis, the development of photosensitizers that specifically provoke mitochondrial dysfunction and consequentially trigger ferroptosis via PDT is of significant interest. To this end, we have designed and synthesized a novel nanoparticle, termed FECTPN, tailored to address this requisite...

Developing effective nanomedicines to cross the blood-brain barrier (BBB) for efficient glioma theranostics is still considered to be a challenging task. Here, we describe the development of macrophage membrane (MM)-coated nanoclusters (NCs) of ultrasmall iron oxide nanoparticles (USIO NPs) with dual pH- and reactive oxygen species (ROS)-responsivenesses for magnetic resonance (MR) imaging and chemotherapy/chemodynamic therapy (CDT) of orthotopic glioma. Surface citrate-stabilized USIO NPs were solvothermally synthesized, sequentially modified with ethylenediamine and phenylboronic acid, and cross-linked with gossypol to form gossypol-USIO NCs (G-USIO NCs), which were further coated with MMs...