Cancer is the second largest cause of death worldwide with the number of new cancer cases predicted to grow significantly in the next decades. Biotechnology and medicine can and should work hand-in-hand to improve cancer diagnosis and treatment efficacy. However, success has been frequently limited, in particular when treating late-stage solid tumors. There still is the need to develop smart and synergistic therapeutic approaches to achieve the synthesis of strong and effective drugs and delivery systems. Much interest has been paid to the development of smart drug delivery systems (drug-loaded particles) that utilize passive targeting, active targeting, and/or stimulus responsiveness strategies. This review will summarize some main ideas about the effect of each strategy and how the combination of some or all of them has shown to be effective. After a brief introduction of current cancer therapies and their limitations, we describe the biological barriers that nanoparticles need to overcome, followed by presenting different types of drug delivery systems to improve drug accumulation in tumors. Then, we describe cancer cell membrane targets that increase cellular drug uptake through active targeting mechanisms. Stimulusresponsive targeting is also discussed by looking at the intra-and extracellular conditions for specific drug release. We include a significant amount of information summarized in tables and figures on nanoparticle-based therapeutics, PEGylated drugs, different ligands for the design of active-targeted systems, and targeting of different organs. We also discuss some still prevailing fundamental limitations of these approaches, eg, by occlusion of targeting ligands.

Cancer is one of the leading health problems we face today. A possible way to develop specific treatments is through the identification and understanding of proteins responsible for the regulation of apoptosis. Apoptosis is a cell suicide that is critically important for organ development and tissue turnover.1 The BCL-2 homology domain (BHD) and BH3-only domain (BOD) are pro-apoptotic proteins that mediate mitochondrial damage, inducing intrinsic pathway cell death. This review wants to explain how BOD and BHD proteins trigger mitochondrial events associated to apoptosis to develop treatments that can promote apoptosis in cancer cells.

Cholesterol (Cho) is a sterol that plays an essential role in the maintenance of biologic cell membranes, and various lipoproteins are its carriers through blood circulation [1]. Some FDA-approved anticancer drugs (i.e., Lipoplatin and Myocet) are conjugated to Cho moieties to improve their pharmacokinetic properties, cellular uptake and target specificity [2]. Recently natural and synthetic sterol compounds have shown a broad spectrum of pharmacological activities [3,4]. Herein, we investigated the anticancer activity of various natural Cho analogs, ie. asiatic acid (AsA), betulinic acid (BeA), oleanolic acid (OleA), ursolic Acid (UrA), lupeol (Lupe) and β-sitosterol (β-Sito) against non-small cell lung adenocarcinoma (A549). We performed theoretical calculations of the biophysicochemical properties, and viability assays in a range of 5–100 μM in A549 cells of these Cho analogs. We used ChemSketch and ChemSpider to determine physical properties, and GraphPad Prism 8 software for the data analysis to determine the inhibitory concentrations at 50% (IC 50 ) of each compound.

Cancer is the second largest cause of death worldwide with the number of new cancer cases predicted to grow significantly in the next decades. Cytotoxic drugs are the main therapy against cancer; however, they are frequently associated with severe side‐effects related to systemic toxicity and lack of tumor specificity. As consequence, the use of proteins as drug carriers has had great impact in the development of new approaches as drug delivery system (DDS) nanoparticles (NPs). For example, Abraxane®, the first FDA‐approved DDS NPs, is composed of serum albumin protein and paclitaxel drug, and has demonstrated higher tumor accumulation, patient toleration, and response rate than the free paclitaxel. Due to this, the aim of this research project is the development of a synergistic DDS NPs using serum albumin (BSA), as the drug's carrier, coupling two cytotoxic drugs: doxorubicin (DOX), and the natural triterpene betulinic acid (BeA). This system BSA[(Dox)(BeA)] was done by using water in oil (W/O)‐like emulsion followed by heat and ultrasonication. To characterize the BSA and Dox concentration in the DDS, colorimetric assays were performed. DDS's size was determined ~ 100 nm using dynamic light scattering. All the developed DDS demonstrated a strong IC50 in the μM range after 24h incubated with lung (A549) and resistant‐ovarian (A2780‐CP20) cancer cells. A complete discussion of the results will be presented. These DDS have potential to minimize drug systemic toxicity and increase drug bioavailability.

The acquired multidrug resistance syndrome (MDRS) is one of the leading causes for the failure of chemotherapy in lung cancer. Recently plant‐derived triterpenoids (eg, cholesterol‐structural analogs) have showed a wide spectrum of pharmacological activities. In addition, in different studies, anticancer agents have been combined to cholesterol moieties to improve their cellular uptake and target specificity. Herein, we investigated the cytotoxic activity of various triterpenoids cholesterol analogs: oleanolic acid (OleA), ursolic acid (UrA), betulinic acid (BeA), asiatic acid (AsA), lupeol (Lupe), stigmasterol (Stg) and β‐sitosterol (β‐Sito) on non‐small lung adenocarcinoma cells (A549) and normal lung cells (MRC5). From our studies, the IC 50 for most of these cholesterol‐analogs were in the low μM range after 24h of incubation. β‐Sito and Stg did not show any significant cytotoxic pattern in this μM range. In addition BeA and OleA showed the highest therapeutic indexes comparing the cytotoxic effect in A549 vs MRC5 cells. Metabolic activity assays were performed to determine the mechanism of action of these natural compounds. Caspases activity and cell membrane integrity assays were performed and all the cytotoxic triterpenoids induced no activation of caspase‐3, and high membrane permeabilization. Gene expression assays of MDRS‐related genes (EGF, VEGF, Pgp, Bcl‐2, P 53 , NDRG1, GLIPR1) demonstrated the downregulation of some of these genes after the incubation with these triterpenoids. These results demonstrated that even slight structural changes in these cholesterol analogs can influence the cytotoxic response and cellular mechanistic pathways. Complete results will be presented. This study opens promising perspectives for further research on the role of phytochemical triterpenoids, which ultimately will contribute to a more rational application in cancer therapy. Support or Funding Information SJB‐Research Center Seed