Delivery Of Chemotherapeutic Agents Research Articles

Design and characterization of Glypican-3 targeted liposomes with cantharidin encapsulation for hepatocellular carcinoma treatment

Targeted delivery of chemotherapeutic agents to the cancerous cells is of fundamental importance and the key step of the targeted delivery system design is to choice a specific receptor. Glypican-3 (GPC3) is a known cell membrane-associated oncofetal proteoglycan that is specifically up-regulated in the fast-growing hepatocarcinoma cells but rarely expressed in the normal healthy liver. Therefore, GPC3 may be a perfect targeting receptor for delivery treatment of hepatocellular carcinoma (HCC). In the present study, a GPC3 specific-targeting nanoliposomal drug delivery system was constructed with GPC3 targeting peptide (named as L5 peptide) modification and anticancer drug cantharidin encapsulation, which aims to realize cantharidin targeted treatment of liver cancer. In our study, nanoliposome specifically targeting GPC3 receptor was successfully constructed with particle size of 127.9 nm and a spherical shape. The targeted liposomes were stable under 4 °C or room temperature for almost 15 days. The drug release from L5-modified liposomes was controlled and delayed. Their targeted delivery properties were characterized by relatively more accumulation in the GPC3 highly expressed HepG2 cells than that of GPC3 lowly expressed Huh-7 cells. The competition results also indicated that the liposomes with L5 peptide modification could competitively bind to GPC3 receptor. Moreover, the liposomes showed colocalization with the lysosome after 3 h incubation. The L5-modified liposomal CTD had an augmented cell growth inhibition and tumor inhibition than that of the free CTD on HepG2 cells and GPC3 highly expressed tumor mice. Our study establishes a new strategy for improving HCC treatment and chemotherapeutic agent targeting delivery.

Intraocular Surgery for Retinoblastoma: An Evaluation of Current Evidence

<b><i>Background:</i></b> Retinoblastoma (Rb) is the most common intraocular malignancy of childhood. The prognosis in Rb directly relates to the spread of disease beyond the eye, particularly to the central nervous system. Therefore, until the recent past, surgically entering an eye with active or recently active Rb was absolutely contraindicated in most centres around the world due to the risk of iatrogenic extraocular spread. <b><i>Summary:</i></b> In this review article, we explore the role of intraocular surgery in Rb. We describe the techniques which have been developed in order to safely deliver chemotherapeutic agents into the eye, both intravitreal and intracameral. We discuss the role of vitrectomy and endoresection for treatment of vitreous seeds and active retinal tumours. In the context of previously treated Rb, we outline various surgical interventions performed to improve visual outcomes or to manage the ocular sequelae of the disease. In particular, we review the various techniques used to maximise the safety of cataract, retinal and glaucoma surgery in children with a history of Rb. <b><i>Key Messages:</i></b> The role of intraocular surgery in Rb is now well established, particularly in the delivery of chemotherapeutic agents or in the presence of previously treated diseases. The role of intraocular surgery in eyes with active Rb is less well established and remains the subject of much debate. However, it is likely that with further development of safer surgical techniques, the indications and modalities will continue to broaden.

Engineered Bacteriophage-Based In Situ Vaccine Remodels a Tumor Microenvironment and Elicits Potent Antitumor Immunity.

In situ vaccines (ISVs) utilize the localized delivery of chemotherapeutic agents or radiotherapy to stimulate the release of endogenous antigens from tumors, thereby eliciting systemic and persistent immune activation. Recently, a bioinspired ISV strategy has attracted tremendous attention due to its features such as an immune adjuvant effect and genetic plasticity. M13 bacteriophages are natural nanomaterials with intrinsic immunogenicity, genetic flexibility, and cost-effectiveness for large-scale production, demonstrating the potential for application in cancer vaccines. In this study, we propose an ISV based on the engineered M13 bacteriophage targeting CD40 (M13CD40) for dendritic cell (DC)-targeted immune stimulation, named H-GM-M13CD40. We induce immunogenic cell death and release tumor antigens through local delivery of (S)-10-hydroxycamptothecin (HCPT), followed by intratumoral injection of granulocyte-macrophage colony stimulating factor (GM-CSF) and M13CD40 to enhance DC recruitment and activation. We demonstrate that this ISV strategy can result in significant accumulation and activation of DCs at the tumor site, reversing the immunosuppressive tumor microenvironment. In addition, H-GM-M13CD40 can synergize with the PD-1 blockade and induce abscopal effects in cold tumor models. Overall, our study verifies the immunogenicity of the engineered M13CD40 bacteriophage and provides a proof of concept that the engineered M13CD40 phage can function as an adjuvant for ISVs.

How Shilajit-Based Nanocarriers Alter Classical Doxorubicin Delivery to Breast Cancer Cells (MCF-7 and ZR-75-1).

Chemotherapy has been ineffective in cancer treatment, and efficient delivery of chemotherapeutic agents remains a challenge. In this study, we developed a doxorubicin-loaded shilajit-based nanocarrier (SHN-Dox) using a nanoprecipitation method to enhance Dox uptake into breast cancer cells (MCF-7 and ZR-75-1). After confirmation of the physicochemical properties of the nanocarriers, the cytotoxic and pro-apoptotic effects of SHN-Dox and the production of reactive oxygen species (ROS) were evaluated on breast cancer cells. SHN-Dox showed a spherical shape with a size of 244 nm and a sustainable release profile of Dox. It exhibited high cytotoxicity against MCF-7 and ZR-75-1 cells, effectively inducing DNA fragmentation in these cells. After 24 h of treatment, SHN-Dox increased the apoptosis rate in MCF-7 cells and raised ROS levels. Therefore, SHN-Dox is a promising carrier that might reduce the side effects of Dox on healthy cells and provide a new strategy for clinical cancer treatment.

FXR1 stabilizes SNORD63 to regulate blood-tumor barrier permeability through SNORD63 mediated 2’-O-methylation of POU6F1

How selectively increase blood-tumor barrier (BTB) permeability is crucial to enhance the delivery of chemotherapeutic agents to brain tumor tissues. In this study, we established in vitro models of the blood-brain barrier (BBB) and BTB using endothelial cells (ECs) co-cultured with human astrocytes (AECs) and glioma cells (GECs), respectively. The findings revealed high expressions of the RNA-binding protein FXR1 and SNORD63 in GECs, where FXR1 was found to bind and stabilize SNORD63. Knockdown of FXR1 resulted in decreased expression of tight-junction-related proteins and increased BTB permeability by down-regulating SNORD63. SNORD63 played a role in mediating the 2’-O-methylation modification of POU6F1 mRNA, leading to the downregulation of POU6F1 protein expression. POU6F1 showed low expression in GECs and acted as a transcription factor to regulate BTB permeability by binding to the promoter regions of ZO-1, occludin, and claudin-5 mRNAs and negatively regulating their expressions. Finally, the targeted regulation of FXR1, SNORD63, and POU6F1 expressions, individually or in combination, effectively enhanced doxorubicin passage through the BTB and induced apoptosis in glioma cells. This study aims to elucidate the underlying mechanism of the FXR1/SNORD63/POU6F1 axis in regulating BTB permeability, offering a novel strategy to improve the efficacy of glioma chemotherapy.

Lauric acid-based thermosensitive delivery system for the treatment of head and neck squamous cell carcinoma

Traditional treatments for head and neck squamous cell carcinoma (HNSCC) such as surgery, radiation therapy, and chemotherapy, often have severe side effects. Local delivery of chemotherapeutic agents can be a promising approach to minimise systemic toxicity and improve efficacy. Lauric acid (LA), was explored as a novel injectable thermosensitive drug reservoir as a depot for sustained release of anticancer drugs to treat HNSCC. LA was characterised in terms of melting temperature and gelation time. The efficacy of LA-based drug formulations was tested in vitro in a HNSCC cell line and in vivo in a mouse model of HNSCC. LA was modified to have a melting point of 38.5 °C and a gelation time of 40 s at 37.5 °C, rendering it suitable for injection at body temperature. LA- based doxorubicin (DOXO) formulation showed slow release with a maximum of 18% release after 3 days. The in vitro study showed that LA enhanced the cytotoxic effect of DOXO. LA combined with DOXO prevented tumour progression and LA alone significantly reduced the original tumour volume compared to the untreated control group. These findings confirmed that LA can function as practical carrier for the local delivery of chemotherapeutics and provides a safe and simple strategy for the delivery of hydrophobic anticancer drugs and warrant further testing in clinical trials.

Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy in Patients With Advanced Ovarian Cancer (OVHIPEC-1): Final Survival Analysis of a Randomised, Controlled, Phase 3 Trial

(Abstracted from Lancet Oncol 2023;24:P1109–P1118) Although the 5-year survival of patients with advanced ovarian cancer has improved, overall survival at 10 years remains approximately 13%. Hyperthermic intraperitoneal chemotherapy (HIPEC) involves the delivery of chemotherapeutic agents directly into the peritoneum in combination with hyperthermia, which enhances penetration and increases sensitivity to platinum compounds by inducing a transient state of homologous recombination deficiency.

Harnessing Nanotechnology: Emerging Strategies for Multiple Myeloma Therapy.

Advances in nanotechnology have provided novel avenues for the diagnosis and treatment of multiple myeloma (MM), a hematological malignancy characterized by the clonal proliferation of plasma cells in the bone marrow. This review elucidates the potential of nanotechnology to revolutionize myeloma therapy, focusing on nanoparticle-based drug delivery systems, nanoscale imaging techniques, and nano-immunotherapy. Nanoparticle-based drug delivery systems offer enhanced drug targeting, reduced systemic toxicity, and improved therapeutic efficacy. We discuss the latest developments in nanocarriers, such as liposomes, polymeric nanoparticles, and inorganic nanoparticles, used for the delivery of chemotherapeutic agents, siRNA, and miRNA in MM treatment. We delve into nanoscale imaging techniques which provide spatial multi-omic data, offering a holistic view of the tumor microenvironment. This spatial resolution can help decipher the complex interplay between cancer cells and their surrounding environment, facilitating the development of highly targeted therapies. Lastly, we explore the burgeoning field of nano-immunotherapy, which employs nanoparticles to modulate the immune system for myeloma treatment. Specifically, we consider how nanoparticles can be used to deliver tumor antigens to antigen-presenting cells, thus enhancing the body's immune response against myeloma cells. In conclusion, nanotechnology holds great promise for improving the prognosis and quality of life of MM patients. However, several challenges remain, including the need for further preclinical and clinical trials to assess the safety and efficacy of these emerging strategies. Future research should also focus on developing personalized nanomedicine approaches, which could tailor treatments to individual patients based on their genetic and molecular profiles.

10097-ACT-6 PHASE 1/2, PROSPECTIVE, INTERNATIONAL MULTI-CENTER STUDY TO ESTABLISH THE SAFETY AND FEASIBILITY OF BLOOD-BRAIN-BARRIER DISRUPTION COMBINED WITH CARBOPLATIN FOR RECURRENT GLIOBLASTOMA; FIRST CLINICAL EXPERIENCE IN JAPAN

Abstract The prognosis for glioblastoma is still very poor despite intensive treatment by surgery, radiation, and chemotherapy. One of the reasons for poor prognosis of glioblastoma is blood-brain-barrier (BBB), which limits the delivery of chemotherapeutic agents to the brain. Focused ultrasound (FUS) therapy is approved for essential tremor and Parkinson disease in Japan and preclinical studies suggest low-intensity focused ultrasound (LIFU) administered with microbubbles (MB) can disrupt BBB and can improve the delivery of chemotherapeutic agents. Our institutions (Osaka University Hospital and Saito Yukoukai Hospital) are the first in Japan to join the international multicenter study to examine the safety and feasibility of BBB disruption by FUS and MB combined with intravenous carboplatin for the treatment of recurrent glioblastoma. We enrolled one patient with recurrent glioblastoma located at left frontal lobe. The patient underwent 4 cycles of treatment during which the disease remained stable by contrast enhanced MRI. After the 4 cycles of treatment, the patient presented with worsening of right hemiparesis and aphasia and terminated protocol treatment because of progressive disease. The progression free survival was 111 days even though the tumor located eloquent area, left frontal lobe. In conclusion, BBB disruption strategies using FUS and MB for the treatment of neuro-oncological disease has potentials to improve the outcome of patients with glioblastoma and many clinical trials will be performed in future.

Engineered exosomes: a promising vehicle in cancer therapy.

During the past few decades, researchers have attempted to discover an effective treatment for cancer. Exosomes are natural nanovesicles released by various cells and play a role in communication between cells. While natural exosomes have high clinical potential, their inherent limitations have prompted researchers to design exosomes with improved therapeutic properties. To achieve this purpose, researchers have undertaken exosome engineering to modify the surface properties or internal composition of exosomes. After these modifications, engineered exosomes can be used as carriers for delivery of chemotherapeutic agents, targeted drug delivery or development of cancer vaccines. The present study provides an overview of exosomes, including their biogenesis, biological functions, isolation techniques, engineering methods, and potential applications in cancer therapy.

Application of Milk Exosomes for Musculoskeletal Health: Talking Points in Recent Outcomes.

Milk is a nutrient-rich food source, and among the various milks, breast milk is a nutrient source provided by mothers to newborns in many mammals. Exosomes are nano-sized membranous extracellular vesicles that play important roles in cell-to-cell communication. Exosomes originate from endogenous synthesis and dietary sources such as milk. Discovered through electron microscopy as floating vesicles, the existence of exosomes in human milk was confirmed owing to a density between 1.10 and 1.18 g/mL in a sucrose gradient corresponding to the known density of exosomes and detection of MHC classes I and II, CD63, CD81, and CD86 on the vesicles. To date, milk exosomes have been used for treating many diseases, including cancers, and are widely proposed as promising carriers for the delivery of chemotherapeutic agents. However, few studies on milk exosomes focus on geriatric health, especially sarcopenia and osteoporosis related to bone and muscle. Therefore, the present study focused on milk exosomes and their cargoes, which are potential candidates for dietary supplements, and when combined with drugs, they can be effective in treating musculoskeletal diseases. In this review, we introduce the basic concepts, including the definition, various sources, and cargoes of milk exosomes, and exosome isolation and characterization methods. Additionally, we review recent literature on the musculoskeletal system and milk exosomes. Since inflammation and oxidative stress underly musculoskeletal disorders, studies reporting the antioxidant and anti-inflammatory properties of milk exosomes are also summarized. Finally, the therapeutic potential of milk exosomes in targeting muscle and bone health is proposed.

Naringin-Dextrin Nanocomposite Abates Diethylnitrosamine/Acetylaminofluorene-Induced Lung Carcinogenesis by Modulating Oxidative Stress, Inflammation, Apoptosis, and Cell Proliferation.

Nanotechnology has proven advantageous in numerous scientific applications, one being to enhance the delivery of chemotherapeutic agents. This present study aims to evaluate the mechanisms underlying the chemopreventive action of naringin-dextrin nanocomposites (Nar-Dx-NCs) against diethylnitrosamine (DEN)/2-acetylaminofluorene (2AAF)-induced lung carcinogenesis in male Wistar rats. DEN was administered intraperitoneally (i.p.) (150 mg/kg/week) for two weeks, followed by the oral administration of 2AAF (20 mg/kg) four times a week for three weeks. Rats receiving DEN/2AAF were concurrently treated with naringin or Nar-Dx-NCs orally at a dose of 10 mg/kg every other day for 24 weeks. Naringin and Nar-Dx-NCs treatments prevented the formation of tumorigenic cells within the alveoli of rats exposed to DEN/2AAF. These findings were associated with a significant decrease in lipid peroxidation, upregulation of antioxidant enzyme (glutathione peroxidase and superoxide dismutase) activity, and enhanced glutathione and nuclear factor erythroid 2-related factor 2 expression in the lungs. Naringin and Nar-Dx-NCs exerted anti-inflammatory actions manifested by a decrease in lung protein expression of tumor necrosis factor-α and interleukin-1β and mRNA expression of interleukin-6, interferon-γ, nuclear factor-κB, and inducible nitric oxide synthase, with a concurrent increase in interleukin-10 expression. The anti-inflammatory effect of Nar-Dx-NCs was more potent than naringin. Regarding the effect on apoptosis, both naringin and Nar-Dx-NCs significantly reduced Bcl-2 and increased Bax and P53 expressions. Moreover, naringin or Nar-Dx-NCs induced a significant decrease in the expression of the proliferator marker, Ki-67, and the effect of Nar-Dx-NCs was more marked. In conclusion, Nar-Dx-NCs improved naringin's preventive action against DEN/2AAF-induced lung cancer and exerted anticarcinogenic effects by suppressing oxidative stress and inflammation and improving apoptotic signal induction and propagation.

Waterborne polyurethane magnetic nanomicelles with magnetically governed functions for breast cancer therapy

Drug delivery strategies aim to maximize a drug's therapeutic efficiency by increasing the drug's concentration at the target site while minimizing delivery to off-target tissues. There is a great deal of interest in using magnetic nanoparticles in combination with applied magnetic fields to selectively control drug accumulation and release in target tissue while minimizing effects on other tissues. In this study, a magnetic targeted drug delivery system based on waterborne polyurethane nanomicelles was prepared by encapsulating hydrophobic doxorubicin (DOX, model drug) and hydrophobic oleic acid-superparamagnetic nanoparticles (SPION-OA) into the hydrophobic core of waterborne polyurethane micelles (CPUM) using the solvent evaporation method. The prepared drug-loaded magnetomicelles (CPUM-DOX-SPION) had a spherical shape with an average diameter of 158 nm. The magnetomicelles showed superparamagnetic properties with excellent magnetic resonance imaging (MRI) contrast effects and T2 relaxation in vitro. In the absence and presence of a magnetic field, the cytocompatibility and cellular uptake of the samples were assessed by MTT assay and flow cytometry, respectively, and the cells were imaged with a confocal microscope. Application of the magnetic field increased cellular cytotoxicity and cellular uptake in association with improved DOX delivery. In addition, the in vivo study of tumor volume showed that tumor growth of the mice group treated with CPUM-DOX-SPION in the presence of an external magnetic field was significantly retarded, with no apparent loss of body weight, compared with the same magnetomicelles in the absence of the magnetic field and with free DOX at the same dose. Moreover, the in vivo MRI experiment indicated the potential of these magnetomicelles as a probe in MRI diagnosis for tumor targeting, and the results showed that magnetically guided delivery of CPUM-SPION magnetomicelles into tumors could significantly improve the targeting efficacy. All the results suggest that the prepared novel magnetomicelles will be promising theranostic systems for effective magnetically guided delivery of chemotherapeutic agents and image-guided personalized medicine.

The safety and utility of low-intensity pulsed ultrasound for effective blood–brain barrier penetration in the treatment of glioblastoma: a scoping review protocol

Abstract Glioblastoma (GBM) is one of the most aggressive central nervous system tumours with suboptimal treatment options and associated poor prognosis. A major impediment to systemic treatment is the limitation of drug delivery to the tumour by the blood-brain barrier (BBB). Several novel techniques to permeate the BBB have been described, however of significant promise is the disruption of the blood brain barrier with low-intensity pulsed ultrasound (LIPU) to facilitate the delivery of varying therapeutic agents. This emerging technique has been demonstrated in clinical studies to enhance delivery of chemotherapeutic agents to the tumour. This study protocol seeks to guide the comprehensive review of literature concerning the safety and utility of LIPU for effective BBB penetration in the treatment of GBM. This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA ScR) guideline 2020. The search strategy was performed on four databases: PubMed, EMBASE, SCOPUS, and Cochrane Central Register of Controlled Trials. All observational and human randomised controlled studies describing the use of LIPU in the treatment of GBM will be included. Excluded studies include non-human randomized control trials, abstract only articles, letters to the editor, conference proceedings. Our outcomes include frequency of LIPU used, duration of intervention, clinical outcomes, complications, and challenges associated with the use of LIPU. This study aims to assess the safety and feasibility of this technique in the management of the GBM and proscribe its use if found effective to improve the outcomes in these patients.

Functionalized and Nonfunctionalized Nanosystems for Mitochondrial Drug Delivery with Metallic Nanoparticles.

Background: The application of metallic nanoparticles as a novel therapeutic tool has significant potential to facilitate the treatment and diagnosis of mitochondria-based disorders. Recently, subcellular mitochondria have been trialed to cure pathologies that depend on their dysfunction. Nanoparticles made from metals and their oxides (including gold, iron, silver, platinum, zinc oxide, and titanium dioxide) have unique modi operandi that can competently rectify mitochondrial disorders. Materials: This review presents insight into the recent research reports on exposure to a myriad of metallic nanoparticles that can alter the dynamic ultrastructure of mitochondria (via altering metabolic homeostasis), as well as pause ATP production, and trigger oxidative stress. The facts and figures have been compiled from more than a hundred PubMed, Web of Science, and Scopus indexed articles that describe the essential functions of mitochondria for the management of human diseases. Result: Nanoengineered metals and their oxide nanoparticles are targeted at the mitochondrial architecture that partakes in the management of a myriad of health issues, including different cancers. These nanosystems not only act as antioxidants but are also fabricated for the delivery of chemotherapeutic agents. However, the biocompatibility, safety, and efficacy of using metal nanoparticles is contested among researchers, which will be discussed further in this review.

Lipid-based nanoparticle-mediated combination therapy for breast cancer management: a comprehensive review.

Breast cancer due to the unpredictable and complex etiopathology combined with the non-availability of any effective drug treatment has become the major root of concern for oncologists globally. The number of women affected by the said disease state is increasing at an alarming rate attributed to environmental and lifestyle changes indicating at the exploration of a novel treatment strategy that can eradicate this aggressive disease. So far, it is treated by promising nanomedicine monotherapy; however, according to the numerous studies conducted, the inadequacy of these nano monotherapies in terms of elevated toxicity and resistance has been reported. This review, therefore, puts forth a new multimodal strategic approach to lipid-based nanoparticle-mediated combination drug delivery in breast cancer, emphasizing the recent advancements. A basic overview about the combination therapy and its index is firstly given. Then, the various nano-based combinations of chemotherapeutics involving the combination delivery of synthetic and herbal agents are discussed along with their examples. Further, the recent exploration of chemotherapeutics co-delivery with small interfering RNA (siRNA) agents has also been explained herein. Finally, a section providing a brief description of the delivery of chemotherapeutic agents with monoclonal antibodies (mAbs) has been presented. From this review, we aim to provide the researchers with deep insight into the novel and much more effective combinational lipid-based nanoparticle-mediated nanomedicines tailored specifically for breast cancer treatment resulting in synergism, enhanced antitumor efficacy, and low toxic effects, subsequently overcoming the hurdles associated with conventional chemotherapy.

SLN Mediate Active Delivery of Gefitinib into A549 Cell Line: Optimization, Biosafety and Cytotoxicity Studies

Background: Conventional administration of chemotherapeutic agents associated with low drug distribution to cancer cells with multiple systemic toxicities. Thus, enhancing the active delivery of chemotherapeutic agents to cancer cells increases drug distribution and internalization to targeted cells with minimal systemic toxicities. Objective and Aim: The current study was designed to prepare and optimize solid lipid nanoparti-cles (SLN) containing stearic acid (SA) that mediate active delivery and uptake of gefitinib (GEF) to cancer cells. Methods: The stability of the prepared Plain-SLN formulations was characterized for 90 days. The most stable formulations were loaded with GEF (GEF-SLN) and subjected to pharmaceutical char-acterization. In-vitro dissolution of GEF-SLN formulations was studied using the dialysis method. Biosafety in the terms of hemocompatibility was investigated using fresh blood samples. Addition-ally, the cytotoxicity of GEF-SLN was examined against the lung cancer cell line (A549). Results: The obtained results showed that the prepared formulations fall in the nanosize range from 114 to 411 nm with a negative zeta-potential value from -17 to -27 mV. The particle size of Plain-SLN formulations was increased when the GEF is incorporated during preparation. Besides, the crystallinity of SA was disordered following the incorporation of GEF. In addition, GEF entrapment efficiency into SLN was 88% with a sustained-release profile of about 75% in 24 h. Additionally, the present results revealed that using surfactants with high drug solubility negatively impacts the stability of SLN formulation. Furthermore, hemocompatibility results revealed that all SLN formu-lations showed insignificant hemolysis (1- 4%) at all concentrations. Moreover, cytotoxicity exami-nations revealed that SLN enhanced the antiprofilated activity of GEF compared to free GEF. Conclusion: These data concluded that SLN is a hopeful approach to enhancing the selective depo-sition of GEF into cancer cells and reducing the lymphatic metastasis of lung cancer.

Design and application of prodrug fluorescent probes for the detection of ovarian cancer cells and release of anticancer drug

Ovarian cancer is a gynecologic malignancy with high mortality. The main reason is that it is detected at an advanced stage due to a lack of early diagnosis and treatment. Therefore, it is of great interest to develop a chemical tool that can visualize ovarian cancer cells in real-time and eliminate them. Unfortunately, probes that can simultaneously monitor both modes of action for the diagnosis and treatment of ovarian cancer have not been developed. Here, we designed a novel prodrug fluorescent probe (YW-OAc) that not only visually tracks cancer cells but also enables the on-demand delivery of chemotherapeutic agents. By β-Gal-mediated glycosidic bond hydrolysis, the fluorescent signal changed from blue to green (signal 1), enabling visual tracking of ovarian cancer cells. Subsequently, the identified cancer cells were subjected to precise light irradiation to induce anticancer drug release accompanied by a fluorescence transition from green to blue (signal 2), enabling real-time information on drug release. Thus, the prodrug fluorescent probe YW-OAc provides comprehensive two-step monitoring during cancer cell recognition and clearance. Notably, YW-OAc exhibited high affinity (Km = 3.74 μM), high selectivity, and low detection limit for β-Gal (0.0035 U/mL). We also demonstrated that YW-OAc can visually trace endogenous β-Gal in different cells and exhibit high phototoxicity in ovarian cancer cells. We hope that the prodrug fluorescent probe YW-OAc, can be used as an effective tool for biomedical diagnosis and treatment.

A comparative study between two methods of delivery of chemotherapeutic agent in patients with bone and soft tissue sarcoma of lower extremity

BackgroundWe aimed to compare the effects of peripherally inserted central catheters (PICC) and implantable venous access devices (TIVADs) in terms of complications and shoulder function in patients with malignant bone and soft tissue tumors of the lower extremities.MethodsWe analyzed 65 cases of TIVADs (chest wall) and 65 cases of PICC at the orthopedic department of the Fourth Hospital of Hebei Medical University between June 2019 and December 2021, which were diagnosed with malignant bone tumors or soft tissue tumors of the lower extremities (tumors had to be relatively sensitive to chemotherapy), received regular chemotherapy, with ≥ 14 cycles (42 weeks). The two groups were compared in terms of catheter indwelling time, catheter-related complications, Constant-Murley shoulder function score, and displacement of the position of the catheter end on the catheterization side.ResultsCompared to the PICC group, at six months after catheterization, the TIVADs group reported better outcomes for catheter indwelling time, catheter-related complications, and Constant-Murley score for the catheterization-side shoulder joint (p < 0.05). The TIVADs group also reported less displacement of the catheter end position after 180° abduction of the catheterization-side shoulder joint (p < 0.05).ConclusionsCompared with PICC, TIVADs can prolong catheter indwelling time, reduce catheter-related complications, and maintain shoulder joint function, which makes it an ideal venous-access approach when providing chemotherapy to patients with malignant bone and soft tissue tumors of the lower extremities.

Gene Reprogramming Armed Macrophage Membrane-Camouflaged Nanoplatform Enhances Bionic Targeted Drug Delivery to Solid Tumor for Synergistic Therapy.

Efficient drug delivery to solid tumors remains a challenge. HER2-positive (HER2+) tumors are an aggressive cancer subtype with a resistance to therapy, high risk of relapse, and poor prognosis. Although nanomedicine technology shows obvious advantages in tumor treatment, its potential clinical translation is still impeded by the unsatisfactory delivery and therapeutic efficacy. In this study, a gene reprogramming macrophage membrane-encapsulated drug-loading nanoplatform was developed for HER2+ cancer therapy based on the co-assembly of poly (lactic-co-glycolic acid) (PLGA) nanoparticles and engineered modified macrophage membranes. In this nanoplatform, near-infrared (NIR) fluorescent dye ICG or chemotherapeutic drug doxorubicin (DOX) was loaded into the PLGA cores, and an anti-HER2 affibody was stably expressed on the membrane of macrophages. In comparison to the nanoparticles with conventional macrophage membrane coating, the ICG/DOX@AMNP nanoparticles armed with anti-HER2 affibody showed excellent HER2-targeting ability both in vitro and in vivo. Small animal imaging studies confirmed the improved pharmacokinetics of drug delivery and specific distribution of the ICG/DOX@AMNPs in HER2+ tumors. Mechanistically, compared with DOX@NPs or DOX@MNPs nanoparticles, DOX@AMNPs exhibited synergistic inhibition of HER2+ cancer cells or mice tumor growth by inducing apoptosis and blocking the PI3K/AKT signaling pathway. Altogether, this study proposes a promising biomimetic nanoplatform for the efficient targeted delivery of chemotherapeutic agents to HER2+ tumors, demonstrating its great potential for solid tumor therapy.