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Development of Responsive Nanoparticles for Cancer Therapy 2.0
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Development of Responsive Nanoparticles for Cancer Therapy 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 22568

Special Issue Editors

Prof. Dr. Jordi Puiggalí

E-Mail Website
Guest Editor
Chemical Engineering Department, Universitat Politècnica de Catalunya, c/Eduard Maristany, 08019 Barcelona, Spain
Interests: structure of synthetic polymers; development of biodegradable polymers; study of nanocomposites; polymer physics; polymer crystallization
Special Issues, Collections and Topics in MDPI journals
Dr. Yin Wang

E-Mail Website
Guest Editor
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
Interests: peptide and peptide-drug conjugates; gasotransmitters delivery and therapy; supramolecular self-assembly; biomaterials; reactive oxygen species
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to reopen the Special Issue concerning “Development of Responsive Nanoparticles for Cancer Therapy” due to the high interest received in the previous edition from scholars, researchers and scientists.

Cancer is the second leading cause of death worldwide with over 10 million cases each year. All typical treatments for malignant tumours (e.g., surgery, radiotherapy, chemotherapy, immunotherapy and hyperthermia) have severe limitations that should be adequately addressed. The use of nanoscale polymeric systems can solve some specific problems, such as, for example, the low specificity or the short blood circulation of drugs used in chemotherapy. Efficient drug encapsulation, the protection capability of the payload from the immune system, specific targeting to tumour sites, enhanced cell penetration, stimuli-sensitivity for drug delivery and live-cell imaging are some of the inherent potentials associated with the use of nanoparticles. The previous Special Issue showed different specific and interesting examples about the use of plasmonic nanoparticles, magnetic liposomes, montmorillonite nanocomposites, uracil-functionalized micelles, ruthenium dendrimers and nanoparticles, based on functionalized graphene oxide, carbon nanotubes, aragonite, hydroxyapatite, gold and iron oxide that merit being expanded or complemented.

This new Special Issue of International Journal of Molecular Sciences will pursue the discussion and presentation of recent advances in the design of nanoparticles for cancer treatment. Furthermore, the issue will provide a comprehensive view of recent developments in Polymer chemistry in cancer treatment.

Prof. Dr. Jordi Puiggalí
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

  • nanoparticles
  • liposomes
  • polymersomes
  • micelles
  • surface functionalization
  • cell targeting
  • stimuli-sensitivity
  • drug delivery
  • therapeutic applications
  • diagnostic applications
  • cancer treatment

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Published Papers (7 papers)

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Research

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17 pages, 2866 KiB  
Article
Erythrocyte-Derived Nanoparticles with Folate Functionalization for Near Infrared Pulsed Laser-Mediated Photo-Chemotherapy of Tumors
by Jenny T. Mac, Raviraj Vankayala, Chi-Hua Lee and Bahman Anvari
Int. J. Mol. Sci. 2022, 23(18), 10295; https://doi.org/10.3390/ijms231810295 - 7 Sep 2022
Cited by 6 | Viewed by 2211
Abstract
Despite its common side effects and varying degrees of therapeutic success, chemotherapy remains the gold standard method for treatment of cancer. Towards developing a new therapeutic approach, we have engineered nanoparticles derived from erythrocytes that contain indocyanine green as a photo-activated agent that [...] Read more.
Despite its common side effects and varying degrees of therapeutic success, chemotherapy remains the gold standard method for treatment of cancer. Towards developing a new therapeutic approach, we have engineered nanoparticles derived from erythrocytes that contain indocyanine green as a photo-activated agent that enables near infrared photothermal heating, and doxorubicin hydrochloride (DOX) as a chemotherapeutic drug. We hypothesize that milliseconds pulsed laser irradiation results in rapid heating and photo-triggered release of DOX, providing a dual photo-chemo therapeutic mechanism for tumor destruction. Additionally, the surface of the nanoparticles is functionalized with folate to target the folate receptor-α on tumor cells to further enhance the therapeutic efficacy. Using non-contract infrared radiometry and absorption spectroscopy, we have characterized the photothermal response and photostability of the nanoparticles to pulsed laser irradiation. Our in vitro studies show that these nanoparticles can mediate photo-chemo killing of SKOV3 ovarian cancer cells when activated by pulsed laser irradiation. We further demonstrate that this dual photo-chemo therapeutic approach is effective in reducing the volume of tumor implants in mice and elicits an apoptotic response. This treatment modality presents a promising approach in destruction of small tumor nodules. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy 2.0)
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15 pages, 6543 KiB  
Article
Biomimetic Keratin-Coated Gold Nanoparticles for Photo-Thermal Therapy in a 3D Bioprinted Glioblastoma Tumor Model
by Maila Chirivì, Claudia Bearzi, Paolo Rosa, Selenia Miglietta, Francesca Petronella, Elena De Falco, Antonella Calogero, Roberto Pani, Vincenzo Petrozza, Giovanni Perotto, Roberto Rizzi and Luciano De Sio
Int. J. Mol. Sci. 2022, 23(17), 9528; https://doi.org/10.3390/ijms23179528 - 23 Aug 2022
Cited by 16 | Viewed by 2790
Abstract
Before entering human clinical studies to evaluate their safety and effectiveness, new drugs and novel medical treatments are subject to extensive animal testing that are expensive and time-consuming. By contrast, advanced technologies enable the development of animal-free models that allow the efficacy of [...] Read more.
Before entering human clinical studies to evaluate their safety and effectiveness, new drugs and novel medical treatments are subject to extensive animal testing that are expensive and time-consuming. By contrast, advanced technologies enable the development of animal-free models that allow the efficacy of innovative therapies to be studied without sacrificing animals, while providing helpful information and details. We report on the powerful combination of 3D bioprinting (3DB) and photo-thermal therapy (PTT) applications. To this end, we realize a 3DB construct consisting of glioblastoma U87-MG cells in a 3D geometry, incorporating biomimetic keratin-coated gold nanoparticles (Ker-AuNPs) as a photo-thermal agent. The resulting plasmonic 3DB structures exhibit a homogeneous cell distribution throughout the entire volume while promoting the localization of Ker-AuNPs within the cells. A 3D immunofluorescence assay and transmission electron microscopy (TEM) confirm the uniform distribution of fluorescent-labeled Ker-AuNPs in the volume and their capability to enter the cells. Laser-assisted (λ = 532 nm) PTT experiments demonstrate the extraordinary ability of Ker-AuNPs to generate heating, producing the highest temperature rise of about 16 °C in less than 2 min. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy 2.0)
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26 pages, 2678 KiB  
Article
Liposomal Formulations of a New Zinc(II) Complex Exhibiting High Therapeutic Potential in a Murine Colon Cancer Model
by Nádia Ribeiro, Melissa Albino, Andreia Ferreira, Cristina Escrevente, Duarte C. Barral, João Costa Pessoa, Catarina Pinto Reis, Maria Manuela Gaspar and Isabel Correia
Int. J. Mol. Sci. 2022, 23(12), 6728; https://doi.org/10.3390/ijms23126728 - 16 Jun 2022
Cited by 14 | Viewed by 2991
Abstract
Colorectal cancer is the second leading cause of cancer-related mortality. Many current therapies rely on chemotherapeutic agents with poor specificity for tumor cells. The clinical success of cisplatin has prompted the research and design of a huge number of metal-based complexes as potential [...] Read more.
Colorectal cancer is the second leading cause of cancer-related mortality. Many current therapies rely on chemotherapeutic agents with poor specificity for tumor cells. The clinical success of cisplatin has prompted the research and design of a huge number of metal-based complexes as potential chemotherapeutic agents. In this study, two zinc(II) complexes, [ZnL2] and [ZnL(AcO)], where AcO is acetate and L is an organic compound combining 8-hydroxyquinoline and a benzothiazole moiety, were developed and characterized. Analytical and spectroscopic studies, namely, NMR, FTIR, and UV-Vis allowed us to establish the complexes’ structures, demonstrating the ligand-binding versatility: tetradentate in [ZnL(AcO)] and bidentate in [ZnL2]. Complexes were screened in vitro using murine and human colon cancer cells cultured in 2D and 3D settings. In 2D cells, the IC50 values were <22 µM, while in 3D settings, much higher concentrations were required. [ZnL(AcO)] displayed more suitable antiproliferative properties than [ZnL2] and was chosen for further studies. Moreover, based on the weak selectivity of the zinc-based complex towards cancer cell lines in comparison to the non-tumorigenic cell line, its incorporation in long-blood-circulating liposomes was performed, aiming to improve its targetability. The resultant optimized liposomal nanoformulation presented an I.E. of 76% with a mean size under 130 nm and a neutral surface charge and released the metal complex in a pH-dependent manner. The antiproliferative properties of [ZnL(AcO)] were maintained after liposomal incorporation. Preliminary safety assays were carried out through hemolytic activity that never surpassed 2% for the free and liposomal forms of [ZnL(AcO)]. Finally, in a syngeneic murine colon cancer mouse model, while free [ZnL(AcO)] was not able to impair tumor progression, the respective liposomal nanoformulation was able to reduce the relative tumor volume in the same manner as the positive control 5-fluorouracil but, most importantly, using a dosage that was 3-fold lower. Overall, our results show that liposomes were able to solve the solubility issues of the new metal-based complex and target it to tumor sites. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy 2.0)
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27 pages, 4180 KiB  
Article
Medicated Scaffolds Prepared with Hydroxyapatite/Streptomycin Nanoparticles Encapsulated into Polylactide Microfibers
by Amirmajid Kadkhodaie-Elyaderani, Maria del Carmen de Lama-Odría, Manuel Rivas, Immaculada Martínez-Rovira, Ibraheem Yousef, Jordi Puiggalí and Luis J. del Valle
Int. J. Mol. Sci. 2022, 23(3), 1282; https://doi.org/10.3390/ijms23031282 - 24 Jan 2022
Cited by 7 | Viewed by 3861
Abstract
The preparation, characterization, and controlled release of hydroxyapatite (HAp) nanoparticles loaded with streptomycin (STR) was studied. These nanoparticles are highly appropriate for the treatment of bacterial infections and are also promising for the treatment of cancer cells. The analyses involved scanning electron microscopy, [...] Read more.
The preparation, characterization, and controlled release of hydroxyapatite (HAp) nanoparticles loaded with streptomycin (STR) was studied. These nanoparticles are highly appropriate for the treatment of bacterial infections and are also promising for the treatment of cancer cells. The analyses involved scanning electron microscopy, dynamic light scattering (DLS) and Z-potential measurements, as well as infrared spectroscopy and X-ray diffraction. Both amorphous (ACP) and crystalline (cHAp) hydroxyapatite nanoparticles were considered since they differ in their release behavior (faster and slower for amorphous and crystalline particles, respectively). The encapsulated nanoparticles were finally incorporated into biodegradable and biocompatible polylactide (PLA) scaffolds. The STR load was carried out following different pathways during the synthesis/precipitation of the nanoparticles (i.e., nucleation steps) and also by simple adsorption once the nanoparticles were formed. The loaded nanoparticles were biocompatible according to the study of the cytotoxicity of extracts using different cell lines. FTIR microspectroscopy was also employed to evaluate the cytotoxic effect on cancer cell lines of nanoparticles internalized by endocytosis. The results were promising when amorphous nanoparticles were employed. The nanoparticles loaded with STR increased their size and changed their superficial negative charge to positive. The nanoparticles’ crystallinity decreased, with the consequence that their crystal sizes reduced, when STR was incorporated into their structure. STR maintained its antibacterial activity, although it was reduced during the adsorption into the nanoparticles formed. The STR release was faster from the amorphous ACP nanoparticles and slower from the crystalline cHAp nanoparticles. However, in both cases, the STR release was slower when incorporated in calcium and phosphate during the synthesis. The biocompatibility of these nanoparticles was assayed by two approximations. When extracts from the nanoparticles were evaluated in cultures of cell lines, no cytotoxic damage was observed at concentrations of less than 10 mg/mL. This demonstrated their biocompatibility. Another experiment using FTIR microspectroscopy evaluated the cytotoxic effect of nanoparticles internalized by endocytosis in cancer cells. The results demonstrated slight damage to the biomacromolecules when the cells were treated with ACP nanoparticles. Both ACP and cHAp nanoparticles were efficiently encapsulated in PLA electrospun matrices, providing functionality and bioactive properties. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy 2.0)
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23 pages, 5747 KiB  
Article
Targeted Nanoparticle Photodynamic Diagnosis and Therapy of Colorectal Cancer
by Nokuphila Winifred Nompumelelo Simelane, Cherie Ann Kruger and Heidi Abrahamse
Int. J. Mol. Sci. 2021, 22(18), 9779; https://doi.org/10.3390/ijms22189779 - 10 Sep 2021
Cited by 22 | Viewed by 3172
Abstract
Colorectal cancer (CRC) is an aggressive cancer that remains a challenge to diagnose and treat. Photodynamic diagnosis (PDD) and therapy (PDT) are novel alternative techniques, which can enhance early diagnosis, as well as elicit tumor cell death. This is accomplished through photosensitizer (PS) [...] Read more.
Colorectal cancer (CRC) is an aggressive cancer that remains a challenge to diagnose and treat. Photodynamic diagnosis (PDD) and therapy (PDT) are novel alternative techniques, which can enhance early diagnosis, as well as elicit tumor cell death. This is accomplished through photosensitizer (PS) mediated fluorescence and cytotoxic reactive oxygen species activation upon laser light irradiation excitation at specific low and high range wavelengths, respectively. However, the lack of PS target tumor tissue specificity often hampers these techniques. This study successfully fabricated a bioactive nanoconjugate, ZnPcS4-AuNP-S-PEG5000-NH2-Anti-GCC mAb (BNC), based upon a polyethylene glycol-gold nanoparticle, which was multi-functionalized with a fluorescent PDT metalated zinc phthalocyanine PS, and specific anti-GCC targeting antibodies, to overcome CRC PDD and PDT challenges. The BNC was found to be stable and showed selectively improved subcellular accumulation within targeted CRC for improved PDD and PDT outcomes in comparison to healthy in vitro cultured cells. Additionally, the BNC reported significantly higher late apoptotic PDT-induced CRC cell death rates (34% ***) when compared to PDT PS administration alone (15% *). These results indicated that the improved PDD and PDT outcomes were due to the specific PS accumulation in CRC cells through nanoparticle carriage and bioactive anti-GCC targeting. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy 2.0)
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14 pages, 2825 KiB  
Article
Structural and Functional Characterizations of Cancer Targeting Nanoparticles Based on Hepatitis B Virus Capsid
by Yunseok Heo, Hyeongseop Jeong, Youngki Yoo, Ji-Hye Yun, Bumhan Ryu, Young-je Cha, Bo-Ram Lee, Ye-Eun Jeon, Jongmin Kim, Sojin Jeong, Eunji Jo, Jae-Sung Woo, Jeewon Lee, Hyun-Soo Cho and Weontae Lee
Int. J. Mol. Sci. 2021, 22(17), 9140; https://doi.org/10.3390/ijms22179140 - 24 Aug 2021
Viewed by 2870
Abstract
Cancer targeting nanoparticles have been extensively studied, but stable and applicable agents have yet to be developed. Here, we report stable nanoparticles based on hepatitis B core antigen (HBcAg) for cancer therapy. HBcAg monomers assemble into spherical capsids of 180 or 240 subunits. [...] Read more.
Cancer targeting nanoparticles have been extensively studied, but stable and applicable agents have yet to be developed. Here, we report stable nanoparticles based on hepatitis B core antigen (HBcAg) for cancer therapy. HBcAg monomers assemble into spherical capsids of 180 or 240 subunits. HBcAg was engineered to present an affibody for binding to human epidermal growth factor receptor 1 (EGFR) and to present histidine and tyrosine tags for binding to gold ions. The HBcAg engineered to present affibody and tags (HAF) bound specifically to EGFR and exterminated the EGFR-overexpressing adenocarcinomas under alternating magnetic field (AMF) after binding with gold ions. Using cryogenic electron microscopy (cryo-EM), we obtained the molecular structures of recombinant HAF and found that the overall structure of HAF was the same as that of HBcAg, except with the affibody on the spike. Therefore, HAF is viable for cancer therapy with the advantage of maintaining a stable capsid form. If the affibody in HAF is replaced with a specific sequence to bind to another targetable disease protein, the nanoparticles can be used for drug development over a wide spectrum. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy 2.0)
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Review

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35 pages, 8424 KiB  
Review
Hydroxyapatite Biobased Materials for Treatment and Diagnosis of Cancer
by María del Carmen De Lama-Odría, Luis J. del Valle and Jordi Puiggalí
Int. J. Mol. Sci. 2022, 23(19), 11352; https://doi.org/10.3390/ijms231911352 - 26 Sep 2022
Cited by 14 | Viewed by 2935
Abstract
Great advances in cancer treatment have been undertaken in the last years as a consequence of the development of new antitumoral drugs able to target cancer cells with decreasing side effects and a better understanding of the behavior of neoplastic cells during invasion [...] Read more.
Great advances in cancer treatment have been undertaken in the last years as a consequence of the development of new antitumoral drugs able to target cancer cells with decreasing side effects and a better understanding of the behavior of neoplastic cells during invasion and metastasis. Specifically, drug delivery systems (DDS) based on the use of hydroxyapatite nanoparticles (HAp NPs) are gaining attention and merit a comprehensive review focused on their potential applications. These are derived from the intrinsic properties of HAp (e.g., biocompatibility and biodegradability), together with the easy functionalization and easy control of porosity, crystallinity and morphology of HAp NPs. The capacity to tailor the properties of DLS based on HAp NPs has well-recognized advantages for the control of both drug loading and release. Furthermore, the functionalization of NPs allows a targeted uptake in tumoral cells while their rapid elimination by the reticuloendothelial system (RES) can be avoided. Advances in HAp NPs involve not only their use as drug nanocarriers but also their employment as nanosystems for magnetic hyperthermia therapy, gene delivery systems, adjuvants for cancer immunotherapy and nanoparticles for cell imaging. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy 2.0)
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