Microfluidic Platform for Generating and Releasing Patient-Derived Cancer Organoids with Diverse Shapes: Insight into Shape-Dependent Tumor Growth.

Multicellular spheroids and patient-derived organoids find many applications in fundamental research, drug discovery, and regenerative medicine. Advances in the understanding and recapitulation of organ functionality and disease development require the generation of complex organoid models, including organoids with diverse morphologies. Microfluidics-based cell culture platforms enable time-efficient confined organoid generation.

A Microfluidic Platform for Evaluating the Internalization of Liposome Drug Carriers in Tumor Spheroids.

The development of in vitro models recapitulating nanoparticle transport under physiological flow conditions is of great importance for predicting the efficacy of nanoparticle drug carriers. Liposomes are extensively used for drug delivery owing to their biocompatibility and biodegradability and the ability to carry both hydrophilic and hydrophobic compounds. Here, we used a library of liposomes with various dimensions and a microfluidic platform comprising a large array of uniformly sized breast cancer spheroids to explore size-dependent liposome internalization and retention in the spheroids under close-to-physiological interstitial conditions.

Nanocolloidal hydrogel mimics the structure and nonlinear mechanical properties of biological fibrous networks.

Fibrous networks formed by biological polymers such as collagen or fibrin exhibit nonlinear mechanical behavior. They undergo strong stiffening in response to weak shear and elongational strains, but soften under compressional strain, in striking difference with the response to the deformation of flexible-strand networks formed by molecules. The nonlinear properties of fibrous networks are attributed to the mechanical asymmetry of the constituent filaments, for which a stretching modulus is significantly larger than the bending modulus.

A Macrophages-Enriched Head and Neck Tumor Spheroid Model to Study Foslip Behavior in Tumor Microenvironment.

Purpose: The tumor microenvironment (TME) is composed of various stromal components, including immune cells such as tumor-associated macrophages (TAMs), which play a crucial role in cancer initiation and progression. TAMs can exhibit either a tumor-suppressive M1 or a tumor-promoting M2 phenotype. First, we aimed to develop a 3D human heterotypic model consisting of head and neck squamous cell carcinoma (HNSCC) cells and different subtypes of macrophages to replicate the interactions between immune cells and cancer cells.

Integrating spheroid-on-a-chip with tubeless rocker platform: A high-throughput biological screening platform.

Spheroid-on-a-chip platforms are emerging as promising in vitro models that enable screening of the efficacy of biologically active ingredients. Generally, the supply of liquids to spheroids occurs in the steady flow mode with the use of syringe pumps; however, the utilization of tubing and connections, especially for multiplexing and high-throughput screening applications, makes spheroid-on-a-chip platforms labor- and cost-intensive. Gravity-induced flow using rocker platforms overcomes these challenges.

Phototoxicity of temoporfin-loaded cyclodextrin nanosponges in stroma-rich three-dimensional models of head and neck cancer.

Photodynamic therapy is a multistage treatment, in which cancerous and precancerous cells are destroyed by light activation of a drug (photosensitizer). For a long time, high cellular uptake of the photosensitizer was an important indication of efficient PDT, while the role of photosensitizer penetration was unexplored. Recently, we have demonstrated that nanosponges based on hypercrosslinked β-cyclodextrin polymer (β-CDp) can increase drug penetration at the cost of their cellular uptake in multicellular spheroids, paving the way for studying the impact of penetration on PDT response.

Printing Structurally Anisotropic Biocompatible Fibrillar Hydrogel for Guided Cell Alignment.

Many fibrous biological tissues exhibit structural anisotropy due to the alignment of fibers in the extracellular matrix. To study the impact of such anisotropy on cell proliferation, orientation, and mobility, it is important to recapitulate and achieve control over the structure of man-made hydrogel scaffolds for cell culture. Here, we report a chemically crosslinked fibrous hydrogel due to the reaction between aldehyde-modified cellulose nanofibers and gelatin.

Nanostructured Temperature Indicator for Cold Chain Logistics.

Food, chemicals, agricultural products, drugs, and vaccines should be transported and stored within an appropriate low-temperature range, following cold chain logistics. Violations of the required temperature regime are generally reported by time-temperature indicators; however, current sensors do not cover a sufficiently broad low-temperature range and may lack thermal and photostability. Here, we report a nanostructured solvatochromic temperature indicator formed from cellulose nanocrystals decorated with carbon dots (C-dots).

Modulation of Temoporfin Distribution in Blood by β-Cyclodextrin Nanoshuttles.

Photodynamic therapy represents a more targeted and less invasive alternative cancer treatment to traditional modalities. Temoporfin, as with many photosensitizers, is given by injection into a vein, and its subsequent fate is largely determined by the binding to plasma proteins and interaction with endothelial and blood cells. Thus, it is essential to be able to control and to alter the biodistribution of temoporfin in blood.

Effect of stroma on the behavior of temoporfin-loaded lipid nanovesicles inside the stroma-rich head and neck carcinoma spheroids.

Background: Despite the highly expected clinical application of nanoparticles (NPs), the translation of NPs from lab to the clinic has been relatively slow. Co-culture 3D spheroids account for the 3D arrangement of tumor cells and stromal components, e.g.

NIR Imaging of the Integrin-Rich Head and Neck Squamous Cell Carcinoma Using Ternary Copper Indium Selenide/Zinc Sulfide-Based Quantum Dots.

The efficient intraoperative identification of cancers requires the development of the bright, minimally-toxic, tumor-specific near-infrared (NIR) probes as contrast agents. Luminescent semiconductor quantum dots (QDs) offer several unique advantages for in vivo cellular imaging by providing bright and photostable fluorescent probes. Here, we present the synthesis of ZnCuInSe/ZnS core/shell QDs emitting in NIR (~750 nm) conjugated to NAVPNLRGDLQVLAQKVART (A20FMDV2) peptide for targeting integrin-rich head and neck squamous cell carcinoma (HNSCC).

Advanced co-culture 3D breast cancer model for investigation of fibrosis induced by external stimuli: optimization study.

Radiation-induced fibrosis (RIF) is the main late radiation toxicity in breast cancer patients. Most of the current 3D in vitro breast cancer models are composed by cancer cells only and are unable to reproduce the complex cellular homeostasis within the tumor microenvironment to study RIF mechanisms. In order to account complex cellular interactions within the tumor microenvironment, an advanced 3D spheroid model, consisting of the luminal breast cancer MCF-7 cells and MRC-5 fibroblasts, was developed.

mTHPC-Loaded Extracellular Vesicles Significantly Improve mTHPC Diffusion and Photodynamic Activity in Preclinical Models.

Extracellular vesicles (EVs), derived from the cell, display a phospholipid bilayer membrane that protects the cargo molecules from degradation and contributes to increasing their stability in the bloodstream and tumor targeting. EVs are interesting in regard to the delivery of photosensitizers (PSs) used in the photodynamic therapy (PDT), as they allow us to overcome the limitations observed with liposomes. In fact, liposomal formulation of meta-tetra(hydroxyphenyl)chlorin (mTHPC) (Foslip), one of the most potent clinically approved PSs, is rapidly destroyed in circulation, thus decreasing in vivo PDT efficacy.

Cyclodextrin nanosponge as a temoporfin nanocarrier: Balancing between accumulation and penetration in 3D tumor spheroids.

As the intertissue delivery of hydrophobic temoporfin (mTHPC) remains inefficient, we propose the use of cyclodextrin-based nanosponges as a smart, advanced system for improved mTHPC delivery. Recently, we demonstrated that cyclodextrins (CDs) allow mTHPC to penetrate into tumor spheroids via a nanoshuttle mechanism. However, the CD complexes were very sensitive to the dilution, thus limiting their translation invivo.

Matryoshka-Type Liposomes Offer the Improved Delivery of Temoporfin to Tumor Spheroids.

The balance between the amount of drug delivered to tumor tissue and the homogeneity of its distribution is a challenge in the efficient delivery of photosensitizers (PSs) in photodynamic therapy (PDT) of cancer. To date, many efforts have been made using various nanomaterials to efficiently deliver temoporfin (mTHPC), one of the most potent photosensitizers. The present study aimed to develop double-loaded matryoshka-type hybrid nanoparticles encapsulating mTHPC/cyclodextrin inclusion complexes in mTHPC-loaded liposomes.

Current state of the nanoscale delivery systems for temoporfin-based photodynamic therapy: Advanced delivery strategies.

Enthusiasm for photodynamic therapy (PDT) as a promising technique to eradicate various cancers has increased exponentially in recent decades. The majority of clinically approved photosensitizers are hydrophobic in nature, thus, the effective delivery of photosensitizers at the targeted site is the main hurdle associated with PDT. Temoporfin (mTHPC, medicinal product name: Foscan®), is one of the most potent clinically approved photosensitizers, is not an exception.

The targeting ability of fluorescent quantum dots to the folate receptor rich tumors.

Background: Quantum dots (QDs) bring new insights in cancer theranostics. Exceptional brightness together with the simple possibility to modify surface with targeting molecules make QDs attractive agents in fluorescence guided surgery and photodynamic therapy. Currently, many targeted QDs have been developed for theranostic purpose.

mTHPC-loaded extracellular vesicles outperform liposomal and free mTHPC formulations by an increased stability, drug delivery efficiency and cytotoxic effect in tridimensional model of tumors.

Efficient photodynamic therapy with meta-tetra(hydroxyphenyl)chlorine requires the application of specific nanoformulations. mTHPC liposomal formulation (Foslip) demonstrated favorable pharmacokinetics properties. However, rapid liposomes destruction in circulation and rapid mTHPC release impedes Foslip applications.

Temoporfin-in-Cyclodextrin-in-Liposome-A New Approach for Anticancer Drug Delivery: The Optimization of Composition.

The main goal of this study was to use hybrid delivery system for effective transportation of temoporfin (-tetrakis(3-hydroxyphenyl)chlorin, mTHPC) to target tissue. We suggested to couple two independent delivery systems (liposomes and inclusion complexes) to achieve drug-in-cyclodextrin-in-liposome (DCL) nanoconstructs. We further optimized the composition of DCLs, aiming to alter in a more favorable way a distribution of temoporfin in tumor tissue.

Fluorescent Nanoparticles for the Guided Surgery of Ovarian Peritoneal Carcinomatosis.

Complete surgical resection is the ideal cure for ovarian peritoneal carcinomatosis, but remains challenging. Fluorescent guided surgery can be a promising approach for precise cytoreduction when appropriate fluorophore is used. In the presence paper, we review already developed near- and short-wave infrared fluorescent nanoparticles, which are currently under investigation for peritoneal carcinomatosis fluorescence imaging.