Nanoparticle-based drug delivery via RBC-hitchhiking for the inhibition of lung metastases growth

BackgroundOsteosarcoma is the most common primary bone tumor and has a peak incidence in adolescence. The prognosis for recurrent and metastatic disease is poor and over one-third of patients with localized disease at presentation will recur after treatment with metastases. LOFU produces non-lethal, transient mechanical and thermal stress to cause protein misfolding, endoplasmic reticulum stress, and induction of the heat shock response (refs). Trabectedin is directly tumoricidal through inhibiting transcription and DNA repair, modulates the tumor microenvironment by selectively depleting M2 macrophages, and inhibits the transcription factor heat shock factor 1 (HSF1) (refs). We hypothesized that combination therapy would synergistically intensify the unfolded protein response and heat shock response to facilitate antigen presenting cell activation and efficient presentation to cytotoxic T cells. To examine this, experiments are being conducted to investigate the effect of LOFU in combination with trabectedin and/or radiation therapy (RT) in a murine model of osteosarcoma.MethodsPalpable (<5 mm) subcutaneous K7M2 murine osteosarcoma tumors in BALB/c mice were treated with a) LOFU, b) trabectedin (intravenous (IV) or intratumoral (IT)), c) LOFU + trabectedin, and d) radiation. Tumor growth (ANOVA (Kruskal-Wallis) with Dunn’s test for multiple comparisons), pulmonary metastases (Fisher’s exact test) and survival (Kaplan-Meier) were measured and analyzed in GraphPad Prism.ResultsMean tumor volume in the combination therapy group (428 mm3) was less than nontreated controls (887 mm3), LOFU alone (670 mm3), trabectedin alone (1218 mm3, p=0.0386). Radiation therapy resulted in complete ablation of the tumors. None of the combination therapy mice had grossly detectable lung metastases at time of death but metastases were present in the trabectedin only (20%), LOFU only (50%), and control (50%) groups (not statistically significant).ConclusionsCombination therapy with trabectedin and LOFU yielded smaller tumor size and fewer pulmonary metastases compared to individual therapies alone.

Download Full-text

Role of Thermal Ablation in Colorectal Cancer Lung Metastases

Cancers ◽

10.3390/cancers13040908 ◽

2021 ◽

Vol 13 (4) ◽

pp. 908

Author(s):

Alexandre Delpla ◽

Thierry de Baere ◽

Eloi Varin ◽

Frederic Deschamps ◽

Charles Roux ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factors ◽

Thermal Ablation ◽

Medical Oncology ◽

Pulmonary Metastases ◽

Lung Metastases ◽

Stereotactic Ablative Radiotherapy ◽

Chest Drainage ◽

Results Of Surgery

Background: Consensus guidelines of the European Society for Medical Oncology (ESMO) (2016) provided recommendations for the management of lung metastases. Thermal ablation appears as a tool in the management of these secondary pulmonary lesions, in the same manner as surgical resection or stereotactic ablative radiotherapy (SABR). Methods: Indications, technical considerations, oncological outcomes such as survival (OS) or local control (LC), prognostic factors and complications of thermal ablation in colorectal cancer lung metastases were reviewed and put into perspective with results of surgery and SABR. Results: LC rates varied from 62 to 91%, with size of the metastasis (<2 cm), proximity to the bronchi or vessels, and size of ablation margins (>5 mm) as predictive factors of LC. Median OS varied between 33 and 68 months. Pulmonary free disease interval <12 months, positive carcinoembryonic antigen, absence of neoadjuvant chemotherapy and uncontrolled extra-pulmonary metastases were poor prognostic factors for OS. While chest drainage for less than 48 h was required in 13 to 47% of treatments, major complications were rare. Conclusions: Thermal ablation of a selected subpopulation of patients with colorectal cancer lung metastases is safe and can provide excellent LC and delay systemic chemotherapy.

Download Full-text

Interstitial syndrome-lung ultrasound B lines: a potential marker for pulmonary metastases? A case series

Italian Journal of Medicine ◽

10.4081/itjm.2018.1009 ◽

2018 ◽

Vol 12 (3) ◽

pp. 223-226 ◽

Cited By ~ 1

Author(s):

Maria Viviana Carlino ◽

Costantino Mancusi ◽

Giovanni De Simone ◽

Filomena Liccardi ◽

Mario Guarino ◽

...

Keyword(s):

Lung Ultrasound ◽

Pulmonary Metastases ◽

Lung Metastases ◽

Point Of Care ◽

Case Series ◽

Point Of Care Ultrasound ◽

Interstitial Syndrome ◽

Potential Marker ◽

Bilateral Lung ◽

Enhanced Computed Tomography

Four patients presented to the Emergency Department with dyspnea and they underwent point-of-care ultrasound. Lung ultrasound showed a diffuse bilateral B-profile pattern-interstitial syndrome, they underwent contrast-enhanced computed tomography scan of thorax that showed multiple bilateral lung metastases. The detection, in a dyspneic patient, of a diffuse Bprofile pattern not attributable to traditional interstitial syndrome conditions (pulmonary fibrosis, acute respiratory distress syndrome, acute pulmonary edema, interstitial pneumonia) could be indicative of multiple pulmonary metastases.

Download Full-text

Ultrasound Microbubbles Enhance the Neuroprotective Effect of Mouse Nerve Growth Factor on Intraocular Hypertension-Induced Neuroretina Damage in Rabbits

Journal of Ophthalmology ◽

10.1155/2016/4235923 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9

Author(s):

Xiaoli Shen ◽

Lina Huang ◽

Dahui Ma ◽

Jun Zhao ◽

Yi Xie ◽

...

Keyword(s):

Drug Delivery ◽

Blood Circulation ◽

Neuroprotective Effect ◽

Whole Body ◽

Destruction Process ◽

Optic Nerve Damage ◽

Neuroprotective Drugs ◽

Target Organs ◽

Whole Body Metabolism ◽

Ultrasound Microbubbles

Ultrasound microbubble combined optic protection drugs have obvious protective effect on optic nerve damage. This way of targeting drug delivery is becoming more simple, not through the whole body metabolism, avoiding drug via blood circulation when facing the decomposition and the environment in the interference and destruction process of drugs, to maximize the guarantee to reach target organs of drug concentration and to reache the maximum therapeutic effect. The technique of ultrasound microbubbles is safe, controllable, nonimmunogenic, and repeatable. It provides us with a novel idea in the administration of neuroprotective drugs.

Download Full-text

Case Report: Bilateral Pneumothoraces Due To Targeted Tumor Therapy With Regorafenib in a Young Woman With Metastatic Colorectal Cancer

10.21203/rs.3.rs-991839/v1 ◽

2021 ◽

Author(s):

Tobias Rachow ◽

Tim Sandhaus ◽

Thomas Ernst ◽

Helmut Schiffl ◽

Susanne M. Lang

Keyword(s):

Colorectal Cancer ◽

Chest Pain ◽

Pulmonary Metastases ◽

Lung Metastases ◽

Tumor Therapy ◽

Tension Pneumothorax ◽

Cancer Case ◽

Pretreated Patient ◽

Breath Sounds ◽

The Right

Abstract Background: Colorectal cancer is one of the most common cancer types, frequently metastasizing into the lungs. Treatment options have been vastly improved over the last years. With the increasing use of targeted therapies novel and rare adverse effects can be seen. In this report, we present the case of recurrent spontaneous bilateral pneumothorax due to fulminant tumor necrosis during the administration of regorafenib in a heavily pretreated patient with multiple lung metastases from colorectal cancer. Case presentation: A 43-year-old woman presented in our oncology department with chest pain and dyspnea. The patient was diagnosed with colorectal cancer seven years earlier and had received chemoradiation, surgery and multiple chemotherapies, before she was started on regorafenib because of progressive pulmonary metastases. Clinical examination revealed no breath sounds in the right hemithorax. The patient was tachycardic and orthopneic. Computed tomography scans demonstrated cavitation of former nodular bilateral pulmonary metastases. After drainage and resolution of the right-sided pneumothorax the patient returned eleven days later with recurrent dyspnea, chest pain and subcutaneous emphysema. Bilateral pneumothoraces were treated with chest tubes. Due to left-sided tension pneumothorax video-assisted thoracoscopy and bilateral pleurodeses were performed. Persistent air leaks with severe pain and pulmonary infiltrates led to the death of the patient. Conclusions: Our case illustrates the effectiveness of regorafenib in a highly pretreated patient. However, in our patient the ensuing cavitation of the multiple nodes led to recurrent pneumothoraces and associated infectious complications. Therefore, special surveillance should be implemented to detect potential transformation of solid pulmonary metastases during treatment with this multi-kinase inhibitor.

Download Full-text

Glutathione-responsive PLGA nanocomplex for dual delivery of doxorubicin and curcumin to overcome tumor multidrug resistance

Nanomedicine ◽

10.2217/nnm-2021-0100 ◽

2021 ◽

Author(s):

Xuandi Lai ◽

Xinran Geng ◽

Mengqing Li ◽

Mengxiong Tang ◽

Qiong Liu ◽

...

Keyword(s):

Drug Delivery ◽

Multidrug Resistance ◽

Blood Circulation ◽

Release Profile ◽

Drug Release Profile ◽

Promising Candidate ◽

Nano Drug Delivery ◽

Mdr Reversal

Aim: This work aims to develop an injectable nano-drug delivery system to overcome tumor multidrug resistance (MDR). Methods: A drug delivery nanoplatform based on PEGylated PLGA with glutathione (GSH) responsivity was constructed for dual delivery of doxorubicin and curcumin (termed DCNP), and its MDR reversal efficiency was studied in vitro and in vivo. Results: The DCNPs exhibited a rapid drug release profile under high GSH concentration and could enhance the cellular uptake and cytotoxicity of doxorubicin to MDR cancer cells. Moreover, the DCNPs showed better biocompatibility, longer blood circulation and enhanced antitumor efficiency compared with free drugs. Conclusion: The GSH-responsive nanocarrier is believed to be a promising candidate for overcoming tumor MDR.

Download Full-text

CD47 Functionalization of Nanoparticles as a Poly(ethylene glycol) Alternative: A Novel Approach to Improve Drug Delivery

Current Drug Targets ◽

10.2174/1389450122666210204203514 ◽

2021 ◽

Vol 22 ◽

Author(s):

Noushin Rezaei Vandchali ◽

Fatemeh Moadab ◽

Eskandar Taghizadeh ◽

Amir Tajbakhsh ◽

Seyed Mohammad Gheibi-hayat

Keyword(s):

Drug Delivery ◽

Ethylene Glycol ◽

Retention Time ◽

Blood Circulation ◽

Regulatory Protein ◽

Reticuloendothelial System ◽

Poly Ethylene Glycol ◽

Drug Delivery Vehicles ◽

Novel Approach ◽

Poly Ethylene

Abstract: Bio-degradable nanoparticles (NPs) have several utilizations as the drug delivery vehicles due to their acceptable bio-availability, lower toxicity, potency for encapsulation and controlled release. Moreover, interaction of the NPs with the macrophages of reticuloendothelial system (RES) may decrease NPs efficacy for medical purposes. The surface of NPs is conventionally neutralized with the molecules such as poly(ethylene glycol) (PEG), as one of the most widely applied stealth polymers, in order to restrict the NPs clearance through the RES system. In fact, these molecules exhibit resistance to the RES clearance and proteins adsorption. It is unfortunate that modifying the PEG has some shortcomings like problems in the synthesis as well as correlation to the immune reaction. The CD47 receptor has been well known as a ‘don’t-eat-me’ molecule on the self-cells' surface. Therefore, the receptor will inhibit phagocytosis via binding to its ligand that is known as the signal regulatory protein α (SIRP-α). Moreover, the CD47 receptor, as one of the biomimetic substances, or its derivative peptides have been used recently on the surface of nanoparticles to inhibit phagocytosis and increase the NPs retention time in the blood circulation. Therefore, this review study examined the CD47 receptor and its role in the immune system as well as the use of the CD47 receptor in coating NPs to increase their retention time in the blood circulation.

Download Full-text

Cell-derived biomimetic nanoparticles as a novel drug delivery system for atherosclerosis: predecessors and perspectives

Regenerative Biomaterials ◽

10.1093/rb/rbaa019 ◽

2020 ◽

Vol 7 (4) ◽

pp. 349-358

Author(s):

Long Yang ◽

Guangchao Zang ◽

Jingwen Li ◽

Xinyue Li ◽

Yuanzhu Li ◽

...

Keyword(s):

Cardiovascular Disease ◽

Drug Delivery ◽

Precision Medicine ◽

Blood Circulation ◽

Drug Delivery Systems ◽

High Morbidity ◽

Whole Cells ◽

Biomimetic Nanoparticles ◽

Novel Drug Delivery System ◽

Novel Drug

Abstract Atherosclerosis is a key mechanism underlying the pathogenesis of cardiovascular disease, which is associated with high morbidity and mortality. In the field of precision medicine for the treatment of atherosclerosis, nanoparticle (NP)-mediated drug delivery systems have great potential, owing to their ability to release treatment locally. Cell-derived biomimetic NPs have attracted extensive attention at present due to their excellent targeting to atherosclerotic inflammatory sites, low immunogenicity and long blood circulation time. Here, we review the utility of cell-derived biomimetic NPs, including whole cells, cell membranes and extracellular vesicles, in the treatment of atherosclerosis.

Download Full-text

Stealth Coating of Nanoparticles in Drug-Delivery Systems

Nanomaterials ◽

10.3390/nano10040787 ◽

2020 ◽

Vol 10 (4) ◽

pp. 787 ◽

Cited By ~ 18

Author(s):

See Yee Fam ◽

Chin Fei Chee ◽

Chean Yeah Yong ◽

Kok Lian Ho ◽

Abdul Razak Mariatulqabtiah ◽

...

Keyword(s):

Drug Delivery ◽

Blood Circulation ◽

Delivery Systems ◽

Mononuclear Phagocyte ◽

Polymer Chains ◽

Cancer Therapies ◽

Drug Actions ◽

Coating Characteristics ◽

Systemic Side Effects ◽

Poly Ethylene

Nanoparticles (NPs) have emerged as a powerful drug-delivery tool for cancer therapies to enhance the specificity of drug actions, while reducing the systemic side effects. Nonetheless, NPs interact massively with the surrounding physiological environments including plasma proteins upon administration into the bloodstream. Consequently, they are rapidly cleared from the blood circulation by the mononuclear phagocyte system (MPS) or complement system, resulting in a premature elimination that will cause the drug release at off-target sites. By grafting a stealth coating layer onto the surface of NPs, the blood circulation half-life of nanomaterials can be improved by escaping the recognition and clearance of the immune system. This review focuses on the basic concept underlying the stealth behavior of NPs by polymer coating, whereby the fundamental surface coating characteristics such as molecular weight, surface chain density as well as conformations of polymer chains are of utmost importance for efficient protection of NPs. In addition, the most commonly used stealth polymers such as poly(ethylene glycol) (PEG), poly(2-oxazoline) (POx), and poly(zwitterions) in developing long-circulating NPs for drug delivery are also thoroughly discussed. The biomimetic strategies, including the cell-membrane camouflaging technique and CD47 functionalization for the development of stealth nano-delivery systems, are highlighted in this review as well.

Download Full-text

Polymeric nanoparticles as carrier for targeted and controlled delivery of anticancer agents

Therapeutic Delivery ◽

10.4155/tde-2019-0044 ◽

2019 ◽

Vol 10 (8) ◽

pp. 527-550 ◽

Cited By ~ 6

Author(s):

Vahid Taghipour-Sabzevar ◽

Tahere Sharifi ◽

Mehrdad Moosazadeh Moghaddam

Keyword(s):

Adverse Effect ◽

Drug Delivery ◽

Controlled Release ◽

Anticancer Agents ◽

Blood Circulation ◽

Enzymatic Degradation ◽

Water Solubility ◽

Polymeric Nanoparticles ◽

Controlled Delivery ◽

Drug Adverse Effect

In recent decades, many novel methods by using nanoparticles (NPs) have been investigated for diagnosis, drug delivery and treatment of cancer. Accordingly, the potential of NPs as carriers is very significant for the delivery of anticancer drugs, because cancer treatment with NPs has led to the improvement of some of the drug delivery limitations such as low blood circulation time and bioavailability, lack of water solubility, drug adverse effect. In addition, the NPs protect drugs against enzymatic degradation and can lead to the targeted and/or controlled release of the drug. The present review focuses on the potential of NPs that can help the targeted and/or controlled delivery of anticancer agents for cancer therapy.

Download Full-text