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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 46453

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Special Issue Editors

Dr. Magdalena Markowicz-Piasecka

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Guest Editor

Department of Pharmaceutical Chemistry, Drug Analysis and radiopharmacy, Medical University of Lodz, 90-151 Lodz, Poland
Interests: anti-cancer therapy; transporters; cancer-related hemostasis disturbances; clotting; drug targeting

Dr. Kristiina Huttunen

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Guest Editor

School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.Box 1627, FI-70211 Kuopio, Finland
Interests: transporter; solute carriers (SLC); ATP-binding cassette (ABC); drug delivery; drug targeting; ADME; pharmacokinetics; toxicokinetics; drug development
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Special Issue Information

Dear Colleagues,

Among the controlled drug delivery technologies, targeted drug delivery has attracted the attention of researchers, as it comprises the systemic delivery of a drug carrier system to specific cell types, tissues, or organs. Targeted drug delivery systems would mainly be beneficial in diseases such as cancers, which are a leading cause of death worldwide. Advancements in omic sciences, analytical procedures, and high-throughput screening in the last two decades have led to the realization that cancer is more complex than was originally conceived. Numerous challenges impede effective cancer treatment and development of effective drugs such as ineffective therapeutic drug concentrations reaching the tumor site, life-threatening side effects caused by nonspecific tissue distribution of anti-neoplastic agents, and acquired resistance of cancer cells upon chemotherapy that triggers cross-resistance to a wide range of different drugs. The complexity of cancers requires the development of very delicate approaches in the course of the drug discovery pipeline.

In line with the challenges raised by the complexity of cancer, the aim of the present thematic issue is to provide state-of-the-art information on novel drug delivery systems in order to enhance the selective uptake of cytotoxic agents by tumor cells and spare normal cells. In this Special Issue, we invite you to contribute both new basic findings about innovative molecularly targeted cancer therapies and entrepreneurial methods of drug delivery in cancer, and your exploratory or confirmatory studies testing novel nanoparticle-based delivery systems or vaccine design against cancer. We are also interested in your critical contributions about potential pitfalls in cancer targeted drug delivery approaches, leading to a comprehensive overview about the current methods for drug delivery.

Dr. Magdalena Markowicz-Piasecka
Dr. Kristiina Huttunen
Guest Editors

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Keywords

anticancer therapy
targeted drug delivery
in vivo testing
drug release
drug carriers
chemoresistance
transporters
solute carriers
biomolecules
nanoparticles
nanotechnology

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Published Papers (12 papers)

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Research

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14 pages, 2992 KiB

Open AccessArticle

HO-3867 Induces Apoptosis via the JNK Signaling Pathway in Human Osteosarcoma Cells

by Peace Wun-Ang Lu, Chia-Hsuan Chou, Jia-Sin Yang, Yi-Hsien Hsieh, Meng-Ying Tsai, Ko-Hsiu Lu and Shun-Fa Yang

Pharmaceutics 2022, 14(6), 1257; https://doi.org/10.3390/pharmaceutics14061257 - 13 Jun 2022

Cited by 14 | Viewed by 2085

Abstract

Metastatic osteosarcoma often results in poor prognosis despite the application of surgical en bloc excision along with chemotherapy. HO-3867 is a curcumin analog that induces cell apoptosis in several cancers, but the apoptotic effect and its mechanisms on osteosarcoma cells are still unknown. After observing the decrease in cellular viability of three human osteosarcoma U2OS, HOS, and MG-63 cell lines, and the induction of cellular apoptosis and arrest in sub-G1 phase in U2OS and HOS cells by HO-3867, the human apoptosis array showed that heme oxygenase (HO)-1 and cleaved caspase-3 expressions had significant increases after HO-3867 treatment in U2OS cells and vice versa for cellular inhibitors of apoptosis (cIAP)1 and X-chromosome-linked IAP (XIAP). Western blot analysis verified the results and showed that HO-3867 activated the initiators of both extrinsic caspase 8 and intrinsic caspase 9, and significantly increased cleaved PARP expression in U2OS and HOS cells. Moreover, with the addition of HO-3867, ERK1/2, and JNK1/2 phosphorylation were increased in U2OS and HOS cells. Using the inhibitor of JNK (JNK in 8), HO-3867’s increases in cleaved caspases 3, 8, and 9 could be expectedly suppressed, indicating that JNK signaling is responsible for both apoptotic pathways, including extrinsic and intrinsic, in U2OS and HOS cells caused by HO-3867. Through JNK signaling, HO-3867 has proven to be effective in causing both extrinsic and intrinsic apoptotic pathways of human osteosarcoma cells. Full article

(This article belongs to the Special Issue Novel Strategies for Cancer Targeted Delivery)

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15 pages, 4066 KiB

Open AccessArticle

A Novel CXCR4-Targeted Diphtheria Toxin Nanoparticle Inhibits Invasion and Metastatic Dissemination in a Head and Neck Squamous Cell Carcinoma Mouse Model

by Elisa Rioja-Blanco, Alberto Gallardo, Irene Arroyo-Solera, Patricia Álamo, Isolda Casanova, Ugutz Unzueta, Naroa Serna, Laura Sánchez-García, Miquel Quer, Antonio Villaverde, Esther Vázquez, Xavier León, Lorena Alba-Castellón and Ramon Mangues

Pharmaceutics 2022, 14(4), 887; https://doi.org/10.3390/pharmaceutics14040887 - 18 Apr 2022

Cited by 6 | Viewed by 2692

Abstract

Loco-regional recurrences and metastasis represent the leading causes of death in head and neck squamous cell carcinoma (HNSCC) patients, highlighting the need for novel therapies. Chemokine receptor 4 (CXCR4) has been related to loco-regional and distant recurrence and worse patient prognosis. In this regard, we developed a novel protein nanoparticle, T22-DITOX-H6, aiming to selectively deliver the diphtheria toxin cytotoxic domain to CXCR4⁺ HNSCC cells. The antimetastatic effect of T22-DITOX-H6 was evaluated in vivo in an orthotopic mouse model. IVIS imaging system was utilized to assess the metastatic dissemination in the mouse model. Immunohistochemistry and histopathological analyses were used to study the CXCR4 expression in the cancer cells, to evaluate the effect of the nanotoxin treatment, and its potential off-target toxicity. In this study, we report that CXCR4⁺ cancer cells were present in the invasive tumor front in an orthotopic mouse model. Upon repeated T22-DITOX-H6 administration, the number of CXCR4⁺ cancer cells was significantly reduced. Similarly, nanotoxin treatment effectively blocked regional and distant metastatic dissemination in the absence of systemic toxicity in the metastatic HNSCC mouse model. The repeated administration of T22-DITOX-H6 clearly abrogates tumor invasiveness and metastatic dissemination without inducing any off-target toxicity. Thus, T22-DITOX-H6 holds great promise for the treatment of CXCR4⁺ HNSCC patients presenting worse prognosis. Full article

(This article belongs to the Special Issue Novel Strategies for Cancer Targeted Delivery)

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17 pages, 3468 KiB

Open AccessArticle

Microfluidics Formulated Liposomes of Hypoxia Activated Prodrug for Treatment of Pancreatic Cancer

by Vidhi M. Shah, Craig Dorrell, Adel Al-Fatease, Brittany L. Allen-Petersen, Yeonhee Woo, Yuliya Bortnyak, Rohi Gheewala, Brett C. Sheppard, Rosalie C. Sears and Adam WG. Alani

Pharmaceutics 2022, 14(4), 713; https://doi.org/10.3390/pharmaceutics14040713 - 26 Mar 2022

Cited by 8 | Viewed by 7808

Abstract

Pancreatic ductal adenocarcinoma (PDAC) presents as an unmet clinical challenge for drug delivery due to its unique hypoxic biology. Vinblastine-N-Oxide (CPD100) is a hypoxia-activated prodrug (HAP) that selectively converts to its parent compound, vinblastine, a potent cytotoxic agent, under oxygen gradient. The study evaluates the efficacy of microfluidics formulated liposomal CPD100 (CPD100Li) in PDAC. CPD100Li were formulated with a size of 95 nm and a polydispersity index of 0.2. CPD100Li was stable for a period of 18 months when freeze-dried at a concentration of 3.55 mg/mL. CPD100 and CPD100Li confirmed selective activation at low oxygen levels in pancreatic cancer cell lines. Moreover, in 3D spheroids, CPD100Li displayed higher penetration and disruption compared to CPD100. In patient-derived 3D organoids, CPD100Li exhibited higher cell inhibition in the organoids that displayed higher expression of hypoxia-inducible factor 1 alpha (HIF1A) compared to CPD100. In the orthotopic model, the combination of CPD100Li with gemcitabine (GEM) (standard of care for PDAC) showed higher efficacy than CPD100Li alone for a period of 90 days. In summary, the evaluation of CPD100Li in multiple cellular models provides a strong foundation for its clinical application in PDAC. Full article

(This article belongs to the Special Issue Novel Strategies for Cancer Targeted Delivery)

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26 pages, 5448 KiB

Open AccessEditor’s ChoiceArticle

Novel Methacrylate-Based Multilayer Nanofilms with Incorporated FePt-Based Nanoparticles and the Anticancer Drug 5-Fluorouracil for Skin Cancer Treatment

by Kristijan Skok, Tanja Zidarič, Kristjan Orthaber, Matevž Pristovnik, Nina Kostevšek, Kristina Žužek Rožman, Sašo Šturm, Lidija Gradišnik, Uroš Maver and Tina Maver

Pharmaceutics 2022, 14(4), 689; https://doi.org/10.3390/pharmaceutics14040689 - 22 Mar 2022

Cited by 11 | Viewed by 3225

Abstract

Despite medical advances, skin-associated disorders continue to pose a unique challenge to physicians worldwide. Skin cancer is one of the most common forms of cancer, with more than one million new cases reported each year. Currently, surgical excision is its primary treatment; however, this can be impractical or even contradictory in certain situations. An interesting potential alternative could lie in topical treatment solutions. The goal of our study was to develop novel multilayer nanofilms consisting of a combination of polyhydroxyethyl methacrylate (PHEMA), polyhydroxypropyl methacrylate (PHPMA), sodium deoxycholate (NaDOC) with incorporated superparamagnetic iron–platinum nanoparticles (FePt NPs), and the potent anticancer drug (5-fluorouracil), for theranostic skin cancer treatment. All multilayer systems were prepared by spin-coating and characterised by atomic force microscopy, infrared spectroscopy, and contact angle measurement. The magnetic properties of the incorporated FePt NPs were evaluated using magnetisation measurement, while their size was determined using transmission electron microscopy (TEM). Drug release performance was tested in vitro, and formulation safety was evaluated on human-skin-derived fibroblasts. Finally, the efficacy for skin cancer treatment was tested on our own basal-cell carcinoma cell line. Full article

(This article belongs to the Special Issue Novel Strategies for Cancer Targeted Delivery)

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13 pages, 3537 KiB

Open AccessEditor’s ChoiceArticle

Molecular Tuning of IR-786 for Improved Tumor Imaging and Photothermal Therapy

by Wonbong Lim, Jae Yong Byun, Gayoung Jo, Eun Jeong Kim, Min Ho Park and Hoon Hyun

Pharmaceutics 2022, 14(3), 676; https://doi.org/10.3390/pharmaceutics14030676 - 19 Mar 2022

Cited by 14 | Viewed by 2594

Abstract

A tumor-targeted near-infrared (NIR) fluorophore CA800Cl was developed based on commercially available IR-786 by modulating its physicochemical properties. IR-786, a hydrophobic cationic heptamethine cyanine fluorophore, was previously recognized as a mitochondria-targeting NIR agent with excellent optical properties. Owing to the poor tumor specificity of IR-786 itself, in vivo studies on tumor-targeted imaging have not yet been investigated. A chloro-cyclohexene ring and indolium side groups on the heptamethine chain are key structural features that improve tumor targetability, owing to better biodistribution and clearance. Thus, IR-786 should be designed to be more soluble in aqueous solutions so that it can preferentially accumulate in the tumor based on the structure-inherent targeting strategy. In this study, we developed a bifunctional NIR fluorophore CA800Cl by incorporating carboxylate moieties in the basic structure of IR-786. This improved its tumor targetability and water solubility, thereby enabling the use of CA800Cl for enhanced photothermal cancer therapy. Full article

(This article belongs to the Special Issue Novel Strategies for Cancer Targeted Delivery)

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21 pages, 3816 KiB

Open AccessArticle

Synthesis and Properties of α-Mangostin and Vadimezan Conjugates with Glucoheptoamidated and Biotinylated 3rd Generation Poly(amidoamine) Dendrimer, and Conjugation Effect on Their Anticancer and Anti-Nematode Activities

by Joanna Markowicz, Stanisław Wołowiec, Wojciech Rode and Łukasz Uram

Pharmaceutics 2022, 14(3), 606; https://doi.org/10.3390/pharmaceutics14030606 - 10 Mar 2022

Cited by 5 | Viewed by 2648

Abstract

α-Mangostin and vadimezan are widely studied potential anticancer agents. Their biological activities may be improved by covalent bonding by amide or ester bonds with the third generation poly(amidoamine) (PAMAM) dendrimer, substituted with α-D-glucoheptono-1,4-lactone and biotin. Thus, conjugates of either ester- (G3^gh4B5V) or amide-linked (G3^2B12gh5V) vadimezan, and equivalents of α-mangostin (G3^gh2B5M and G3^2B12gh5M, respectively), were synthesized, characterized and tested in vitro against cancer cells: U-118 MG glioma, SCC-15 squamous carcinoma, and BJ normal human fibroblasts growth, as well as against C. elegans development. α-Mangostin cytotoxicity, stronger than that of Vadimezan, was increased (by 2.5–9-fold) by conjugation with the PAMAM dendrimer (with the amide-linking being slightly more effective), and the strongest effect was observed with SCC-15 cells. Similar enhancement of toxicity resulting from the drug conjugation was observed with C. elegans. Vadimezan (up to 200 µM), as well as both its dendrimer conjugates, was not toxic against both the studied cells and nematodes. It showed an antiproliferative effect against cancer cells at concentrations ≥100 µM. This effect was significantly enhanced after conjugation of the drug with the dendrimer via the amide, but not the ester bond, with G3^2B12gh5V inhibiting the proliferation of SCC-15 and U-118 MG cells at concentrations ≥4 and ≥12 μM, respectively, without a visible effect in normal BJ cells. Thus, the drug delivery system based on the PAMAM G3 dendrimer containing amide bonds, partially-blocked amino groups on the surface, larger particle diameter and higher zeta potential can be a useful tool to improve the biological properties of transported drug molecules. Full article

(This article belongs to the Special Issue Novel Strategies for Cancer Targeted Delivery)

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19 pages, 5741 KiB

Open AccessArticle

Carboxyl-Functionalized Carbon Nanotubes Loaded with Cisplatin Promote the Inhibition of PI3K/Akt Pathway and Suppress the Migration of Breast Cancer Cells

by Madalina Andreea Badea, Mihaela Balas, Mariana Prodana, Florentina Gina Cojocaru, Daniela Ionita and Anca Dinischiotu

Pharmaceutics 2022, 14(2), 469; https://doi.org/10.3390/pharmaceutics14020469 - 21 Feb 2022

Cited by 10 | Viewed by 2418

Abstract

PI3K/Akt signaling is one of the most frequently dysregulated pathways in cancer, including triple-negative breast cancer. With considerable roles in tumor growth and proliferation, this pathway is studied as one of the main targets in controlling the therapies’ efficiency. Nowadays, the development of nanoparticle–drug conjugates attracts a great deal of attention due to the advantages they provide in cancer treatment. Hence, the main purpose of this study was to design a nanoconjugate based on single-walled carbon nanotubes functionalized with carboxyl groups (SWCNT-COOH) and cisplatin (CDDP) and to explore the potential of inhibiting the PI3K/Akt signaling pathway. MDA-MB-231 cells were exposed to various doses (0.01–2 µg/mL SWCNT-COOH and 0.00632–1.26 µg/mL CDDP) of SWCNT-COOH-CDDP and free components for 24 and 48 h. In vitro biological tests revealed that SWCNT-COOH-CDDP had a high cytotoxic effect, as shown by a time-dependent decrease in cell viability and the presence of a significant number of dead cells in MDA-MB-231 cultures at higher doses. Moreover, the nanoconjugates induced the downregulation of PI3K/Akt signaling, as revealed by the decreased expression of PI3K and p-Akt in parallel with PTEN activation, the promotion of Akt protein degradation, and inhibition of tumor cell migration. Full article

(This article belongs to the Special Issue Novel Strategies for Cancer Targeted Delivery)

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Review

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15 pages, 1820 KiB

Open AccessReview

The Potential of Topoisomerase Inhibitor-Based Antibody–Drug Conjugates

by Seungmin Han, Kwang Suk Lim, Brody J. Blackburn, Jina Yun, Charles W. Putnam, David A. Bull and Young-Wook Won

Pharmaceutics 2022, 14(8), 1707; https://doi.org/10.3390/pharmaceutics14081707 - 16 Aug 2022

Cited by 16 | Viewed by 5291

Abstract

DNA topoisomerases are essential enzymes that stabilize DNA supercoiling and resolve entanglements. Topoisomerase inhibitors have been widely used as anti-cancer drugs for the past 20 years. Due to their selectivity as topoisomerase I (TOP1) inhibitors that trap TOP1 cleavage complexes, camptothecin and its derivatives are promising anti-cancer drugs. To increase accumulation of TOP1 inhibitors in cancer cells through the targeting of tumors, TOP1 inhibitor antibody–drug conjugates (TOP1-ADC) have been developed and marketed. Some TOP1-ADCs have shown enhanced therapeutic efficacy compared to prototypical anti-cancer ADCs, such as T-DM1. Here, we review various types of camptothecin-based TOP1 inhibitors and recent developments in TOP1-ADCs. We then propose key points for the design and construction of TOP1-ADCs. Finally, we discuss promising combinatorial strategies, including newly developed approaches to maximizing the therapeutic potential of TOP1-ADCs. Full article

(This article belongs to the Special Issue Novel Strategies for Cancer Targeted Delivery)

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24 pages, 2467 KiB

Open AccessEditor’s ChoiceReview

Controlled-Release Nanosystems with a Dual Function of Targeted Therapy and Radiotherapy in Colorectal Cancer

by Pedro Cruz-Nova, Alejandra Ancira-Cortez, Guillermina Ferro-Flores, Blanca Ocampo-García and Brenda Gibbens-Bandala

Pharmaceutics 2022, 14(5), 1095; https://doi.org/10.3390/pharmaceutics14051095 - 20 May 2022

Cited by 11 | Viewed by 3408

Abstract

Nanoparticles are excellent platforms for several biomedical applications, including cancer treatment. They can incorporate different molecules to produce combinations of chemotherapeutic agents, radionuclides, and targeting molecules to improve the therapeutic strategies against cancer. These specific nanosystems are designed to have minimal side effects on healthy cells and better treatment efficacy against cancer cells when compared to chemotherapeutics, external irradiation, or targeted radiotherapy alone. In colorectal cancer, some metal and polymeric nanoparticle platforms have been used to potentialize external radiation therapy and targeted drug delivery. Polymeric nanoparticles, liposomes, albumin-based nanoparticles, etc., conjugated with PEG and/or HLA, can be excellent platforms to increase blood circulation time and decrease side effects, in addition to the combination of chemo/radiotherapy, which increases therapeutic efficacy. Additionally, radiolabeled nanoparticles have been conjugated to target specific tissues and are mainly used as agents for diagnosis, drug/gene delivery systems, or plasmonic photothermal therapy enhancers. This review aims to analyze how nanosystems are shaping combinatorial therapy and evaluate their status in the treatment of colorectal cancer. Full article

(This article belongs to the Special Issue Novel Strategies for Cancer Targeted Delivery)

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26 pages, 3004 KiB

Open AccessEditor’s ChoiceReview

Advances in the Synthesis and Application of Magnetic Ferrite Nanoparticles for Cancer Therapy

by Seipati Rosemary Mokhosi, Wendy Mdlalose, Amos Nhlapo and Moganavelli Singh

Pharmaceutics 2022, 14(5), 937; https://doi.org/10.3390/pharmaceutics14050937 - 26 Apr 2022

Cited by 46 | Viewed by 5302

Abstract

Cancer is among the leading causes of mortality globally, with nearly 10 million deaths in 2020. The emergence of nanotechnology has revolutionised treatment strategies in medicine, with rigorous research focusing on designing multi-functional nanoparticles (NPs) that are biocompatible, non-toxic, and target-specific. Iron-oxide-based NPs have been successfully employed in theranostics as imaging agents and drug delivery vehicles for anti-cancer treatment. Substituted iron-oxides (MFe₂O₄) have emerged as potential nanocarriers due to their unique and attractive properties such as size and magnetic tunability, ease of synthesis, and manipulatable properties. Current research explores their potential use in hyperthermia and as drug delivery vehicles for cancer therapy. Significantly, there are considerations in applying iron-oxide-based NPs for enhanced biocompatibility, biodegradability, colloidal stability, lowered toxicity, and more efficient and targeted delivery. This review covers iron-oxide-based NPs in cancer therapy, focusing on recent research advances in the use of ferrites. Methods for the synthesis of cubic spinel ferrites and the requirements for their considerations as potential nanocarriers in cancer therapy are discussed. The review highlights surface modifications, where functionalisation with specific biomolecules can deliver better efficiency. Finally, the challenges and solutions for the use of ferrites in cancer therapy are summarised. Full article

(This article belongs to the Special Issue Novel Strategies for Cancer Targeted Delivery)

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26 pages, 4997 KiB

Open AccessEditor’s ChoiceReview

Nanotheranostics for Image-Guided Cancer Treatment

by Isabel S. Dennahy, Zheng Han, William M. MacCuaig, Hunter M. Chalfant, Anna Condacse, Jordan M. Hagood, Juan C. Claros-Sorto, Wajeeha Razaq, Jennifer Holter-Chakrabarty, Ronald Squires, Barish H. Edil, Ajay Jain and Lacey R. McNally

Pharmaceutics 2022, 14(5), 917; https://doi.org/10.3390/pharmaceutics14050917 - 22 Apr 2022

Cited by 20 | Viewed by 4215

Abstract

Image-guided nanotheranostics have the potential to represent a new paradigm in the treatment of cancer. Recent developments in modern imaging and nanoparticle design offer an answer to many of the issues associated with conventional chemotherapy, including their indiscriminate side effects and susceptibility to drug resistance. Imaging is one of the tools best poised to enable tailoring of cancer therapies. The field of image-guided nanotheranostics has the potential to harness the precision of modern imaging techniques and use this to direct, dictate, and follow site-specific drug delivery, all of which can be used to further tailor cancer therapies on both the individual and population level. The use of image-guided drug delivery has exploded in preclinical and clinical trials although the clinical translation is incipient. This review will focus on traditional mechanisms of targeted drug delivery in cancer, including the use of molecular targeting, as well as the foundations of designing nanotheranostics, with a focus on current clinical applications of nanotheranostics in cancer. A variety of specially engineered and targeted drug carriers, along with strategies of labeling nanoparticles to endow detectability in different imaging modalities will be reviewed. It will also introduce newer concepts of image-guided drug delivery, which may circumvent many of the issues seen with other techniques. Finally, we will review the current barriers to clinical translation of image-guided nanotheranostics and how these may be overcome. Full article

(This article belongs to the Special Issue Novel Strategies for Cancer Targeted Delivery)

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14 pages, 1236 KiB

Open AccessReview

Sequential Drug Delivery in Targeted Cancer Therapy

by Han Yu, Na Ning, Xi Meng, Chuda Chittasupho, Lingling Jiang and Yunqi Zhao

Pharmaceutics 2022, 14(3), 573; https://doi.org/10.3390/pharmaceutics14030573 - 5 Mar 2022

Cited by 18 | Viewed by 3115

Abstract

Cancer is a major public health problem and one of the leading causes of death. However, traditional cancer therapy may damage normal cells and cause side effects. Many targeted drug delivery platforms have been developed to overcome the limitations of the free form of therapeutics and biological barriers. The commonly used cancer cell surface targets are CD44, matrix metalloproteinase-2, folate receptors, etc. Once the drug enters the cell, active delivery of the drug molecule to its final destination is still preferred. The subcellular targeting strategies include using glucocorticoid receptors for nuclear targeting, negative mitochondrial membrane potential and N-acetylgalactosaminyltransferase for Golgi apparatus targeting, etc. Therefore, the most effective way to deliver therapeutic agents is through a sequential drug delivery system that simultaneously achieves cellular- and subcellular-level targeting. The dual-targeting delivery holds great promise for improving therapeutic effects and overcoming drug resistance. This review classifies sequential drug delivery systems based on final targeted organelles. We summarize different targeting strategies and mechanisms and gave examples of each case. Full article

(This article belongs to the Special Issue Novel Strategies for Cancer Targeted Delivery)

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